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Therapeutic effects of histone deacetylase inhibitors on kidney disease

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Abstract

Increasing evidence has shown the involvement of histone deacetylases (HDACs) in the development and progression of various renal diseases, highlighting its inhibition as a promising therapeutic strategy to prevent kidney diseases. Accordingly, numerous studies have shown that HDAC inhibitors protect the kidneys from various diseases through their effects on multiple pathways, such as suppression of transforming growth factor-β signaling pathway and nuclear factor-κB signaling pathways, augmentation of apoptosis, and inhibition of angiogenesis. To develop more effective and less toxic isoform-selective HDAC inhibitors and further improve clinical outcomes, it is necessary to identify and understand the mechanisms involved in the pathogenesis and progression of renal diseases. This review focuses on the roles of HDAC inhibitors and the mechanisms involved in their therapeutic effects in experimental models of kidney diseases including glomerulosclerosis, tubulointerstitial fibrosis, glomerular and tubulointerstitial inflammation, lupus nephritis, polycystic kidney disease, and renal cell carcinoma (RCC).

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References

  • Abbas T, Dutta A (2009) p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 9:400–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Abecassis M, Bartlett ST, Collins AJ, Davis CL, Delmonico FL, Friedewald JJ, Hays R, Howard A, Jones E, Leichtman AB, Merion RM, Metzger RA, Pradel F, Schweitzer EJ, Velez RL, Gaston RS (2008) Kidney transplantation as primary therapy for end-stage renal disease: a National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQITM) conference. Clin J Am Soc Nephrol 3:471–480

    Article  PubMed  PubMed Central  Google Scholar 

  • Advani A, Huang Q, Thai K, Advani SL, White KE, Kelly DJ, Yuen DA, Connelly KA, Marsden PA, Gilbert RE (2011) Long-term administration of the histone deacetylase inhibitor vorinostat attenuates renal injury in experimental diabetes through an endothelial nitric oxide synthase-dependent mechanism. Am J Pathol 178:2205–2214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Altucci L, Gronemeyer H (2001) The promise of retinoids to fight against cancer. Nat Rev Cancer 1:181–193

    Article  CAS  PubMed  Google Scholar 

  • Amengual JE, Prabhu SA, Lombardo M, Zullo K, Johannet PM, Gonzalez Y, Scotto L, Serrano XJ, Wei Y, Duong J, Nandakumar R, Cremers S, Verma A, Elemento O, O’Connor OA (2017) Mechanisms of acquired drug resistance to the HDAC6 selective inhibitor ricolinostat reveals rational drug-drug combination with ibrutinib. Clin Cancer Res 23:3084–3096

    Article  CAS  PubMed  Google Scholar 

  • Andrawes MB, Xu X, Liu H, Ficarro SB, Marto JA, Aster JC, Blacklow SC (2013) Intrinsic selectivity of notch 1 for delta-like 4 over delta-like 1. J Biol Chem 288:25477–25489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asanuma K, Mundel P (2003) The role of podocytes in glomerular pathobiology. Clin Exp Nephrol 7:255–259

    Article  CAS  PubMed  Google Scholar 

  • Bali P, Pranpat M, Bradner J, Balasis M, Fiskus W, Guo F, Rocha K, Kumaraswamy S, Boyapalle S, Atadja P, Seto E, Bhalla K (2005) Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem 280:26729–26734

    Article  CAS  PubMed  Google Scholar 

  • Banerji U, van Doorn L, Papadatos-Pastos D, Kristeleit R, Debnam P, Tall M, Stewart A, Raynaud F, Garrett MD, Toal M, Hooftman L, De Bono JS, Verweij J, Eskens FA (2012) A phase I pharmacokinetic and pharmacodynamic study of CHR-3996, an oral class I selective histone deacetylase inhibitor in refractory solid tumors. Clin Cancer Res 18:2687–2694

    Article  CAS  PubMed  Google Scholar 

  • Beier UH, Akimova T, Liu Y, Wang L, Hancock WW (2011) Histone/protein deacetylases control Foxp3 expression and the heat shock response of T-regulatory cells. Curr Opin Immunol 23:670–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berthier CC, Zhang H, Schin M, Henger A, Nelson RG, Yee B, Boucherot A, Neusser MA, Cohen CD, Carter-Su C, Argetsinger LS, Rastaldi MP, Brosius FC, Kretzler M (2009) Enhanced expression of Janus kinase-signal transducer and activator of transcription pathway members in human diabetic nephropathy. Diabetes 58:469–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertos NR, Wang AH, Yang XJ (2001) Class II histone deacetylases: structure, function, and regulation. Biochem Cell Biol 79:243–252

    Article  CAS  PubMed  Google Scholar 

  • Bertrand P (2010) Inside HDAC with HDAC inhibitors. Eur J Med Chem 45:2095–2116

    Article  CAS  PubMed  Google Scholar 

  • Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S, Kato H, Pullman J, Gessler M, Haase VH, Susztak K (2010) Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest 120:4040–4054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brilli LL, Swanhart LM, de Caestecker MP, Hukriede NA (2013) HDAC inhibitors in kidney development and disease. Pediatr Nephrol 28:1909–1921

    Article  PubMed  Google Scholar 

  • Brosius FC 3rd, He JC (2015) JAK inhibition and progressive kidney disease. Curr Opin Nephrol Hypertens 24:88–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broude EV, Swift ME, Vivo C, Chang BD, Davis BM, Kalurupalle S, Blagosklonny MV, Roninson IB (2007) p21(Waf1/Cip1/Sdi1) mediates retinoblastoma protein degradation. Oncogene 26:6954–6958

    Article  CAS  PubMed  Google Scholar 

  • Cao Y, Semanchik N, Lee SH, Somlo S, Barbano PE, Coifman R, Sun Z (2009) Chemical modifier screen identifies HDAC inhibitors as suppressors of PKD models. Proc Natl Acad Sci USA 106:21819–21824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carafa V, Rotili D, Forgione M, Cuomo F, Serretiello E, Hailu GS, Jarho E, Lahtela-Kakkonen M, Mai A, Altucci L (2016) Sirtuin functions and modulation: from chemistry to the clinic. Clin Epigenetics 8:61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cargnello M, Roux PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75:50–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cebotaru L, Liu Q, Yanda MK, Boinot C, Outeda P, Huso DL, Watnick T, Guggino WB, Cebotaru V (2016) Inhibition of histone deacetylase 6 activity reduces cyst growth in polycystic kidney disease. Kidney Int 90:90–99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cha TL, Chuang MJ, Wu ST, Sun GH, Chang SY, Yu DS, Huang SM, Huan SK, Cheng TC, Chen TT, Fan PL, Hsiao PW (2009) Dual degradation of aurora A and B kinases by the histone deacetylase inhibitor LBH589 induces G2-M arrest and apoptosis of renal cancer cells. Clin Cancer Res 15:840–850

    Article  CAS  PubMed  Google Scholar 

  • Chang JW, Kim H, Baek CH, Lee RB, Yang WS, Lee SK (2016) Up-regulation of SIRT1 reduces endoplasmic reticulum stress and renal fibrosis. Nephron 133:116–128

    Article  CAS  PubMed  Google Scholar 

  • Choi SY, Kee HJ, Kurz T, Hansen FK, Ryu Y, Kim GR, Lin MQ, Jin L, Piao ZH, Jeong MH (2016) Class IHDACs specifically regulate E-cadherin expression in human renal epithelial cells. J Cell Mol Med 20:2289–2298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi SY, Ryu Y, Kee HJ, Cho SN, Kim GR, Cho JY, Kim HS, Kim IK, Jeong MH (2015) Tubastatin A suppresses renal fibrosis via regulation of epigenetic histone modification and Smad3-dependent fibrotic genes. Vascul Pharmacol 72:130–140

    Article  CAS  PubMed  Google Scholar 

  • Chun P (2015) Histone deacetylase inhibitors in hematological malignancies and solid tumors. Arch Pharm Res. 38:933–949

    Article  CAS  PubMed  Google Scholar 

  • ClinicalTrials.gov. http://clinicaltrials.gov. Accessed 26 Oct 2017

  • Cooper SJ, von Roemeling CA, Kang KH, Marlow LA, Grebe SK, Menefee ME, Tun HW, Colon-Otero G, Perez EA, Copland JA (2012) Reexpression of tumor suppressor, sFRP1, leads to antitumor synergy of combined HDAC and methyltransferase inhibitors in chemoresistant cancers. Mol Cancer Ther 11:2105–2115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coqueret O, Gascan H (2000) Functional interaction of STAT3 transcription factor with the cell cycle inhibitor p21WAF1/CIP1/SDI1. J Biol Chem 275:18794–18800

    Article  CAS  PubMed  Google Scholar 

  • Dai Q, Liu J, Du YL, Hao X, Ying J, Tan Y, He LQ, Wang WM, Chen N (2016) Histone deacetylase inhibitors attenuate P-aIgA1-induced cell proliferation and extracellular matrix synthesis in human renal mesangial cells in vitro. Acta Pharmacol Sin 37:228–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749

    Article  PubMed  PubMed Central  Google Scholar 

  • Dong W, Jia Y, Liu X, Zhang H, Li T, Huang W, Chen X, Wang F, Sun W, Wu H (2017) Sodium butyrate activates NRF2 to ameliorate diabetic nephropathy possibly via inhibition of HDAC. J Endocrinol 232:71–83

    Article  CAS  PubMed  Google Scholar 

  • Drugs@FDA. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed 26 Oct 2017

  • Fan LX, Li X, Magenheimer B, Calvet JP, Li X (2012) Inhibition of histone deacetylases targets the transcription regulator Id2 to attenuate cystic epithelial cell proliferation. Kidney Int 81:76–85

    Article  CAS  PubMed  Google Scholar 

  • Fath DM, Kong X, Liang D, Lin Z, Chou A, Jiang Y, Fang J, Caro J, Sang N (2006) Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha. J Biol Chem 281:13612–13619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fournel M, Bonfils C, Hou Y, Yan PT, Trachy-Bourget MC, Kalita A, Liu J, Lu AH, Zhou NZ, Robert MF, Gillespie J, Wang JJ, Ste-Croix H, Rahil J, Lefebvre S, Moradei O, Delorme D, Macleod AR, Besterman JM, Li Z (2008) MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol Cancer Ther 7:759–768

    Article  CAS  PubMed  Google Scholar 

  • Freidkin I, Herman M, Tobar A, Chagnac A, Ori Y, Korzets A, Gafter U (2010) Effects of histone deacetylase inhibitors on rat mesangial cells. Am J Physiol Renal Physiol 298:F426–F434

    Article  CAS  PubMed  Google Scholar 

  • Fritzsche FR, Weichert W, Roske A, Gekeler V, Beckers T, Stephan C, Jung K, Scholman K, Denkert C, Dietel M, Kristiansen G (2008) Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer. BMC Cancer 8:381

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gao L, Cueto MA, Asselbergs F, Atadja P (2002) Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem 277:25748–25755

    Article  CAS  PubMed  Google Scholar 

  • Gilbert RE, Huang Q, Thai K, Advani SL, Lee K, Yuen DA, Connelly KA, Advani A (2011) Histone deacetylase inhibition attenuates diabetes-associated kidney growth: potential role for epigenetic modification of the epidermal growth factor receptor. Kidney Int 79:1312–1321

    Article  CAS  PubMed  Google Scholar 

  • Grynberg K, Ma FY, Nikolic-Paterson DJ (2017) The JNK signaling pathway in renal fibrosis. Front Physiol 8:829

    Article  PubMed  PubMed Central  Google Scholar 

  • Gumz ML, Zou H, Kreinest PA, Childs AC, Belmonte LS, LeGrand SN, Wu KJ, Luxon BA, Sinha M, Parker AS, Sun LZ, Ahlquist DA, Wood CG, Copland JA (2007) Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma. Clin Cancer Res 13:4740–4749

    Article  CAS  PubMed  Google Scholar 

  • Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10:32–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hainsworth JD, Infante JR, Spigel DR, Arrowsmith ER, Boccia RV, Burris HA (2011) A phase II trial of panobinostat, a histone deacetylase inhibitor, in the treatment of patients with refractory metastatic renal cell carcinoma. Cancer Invest 29:451–455

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa K, Wakino S, Yoshioka K, Tatematsu S, Hara Y, Minakuchi H, Washida N, Tokuyama H, Hayashi K, Itoh H (2008) Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression. Biochem Biophys Res Commun 372:51–56

    Article  CAS  PubMed  Google Scholar 

  • Hoesel B, Schmid JA (2013) The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer 12:86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061

    Article  CAS  PubMed  Google Scholar 

  • Hricik DE (2015) Transplant immunology and immunosuppression: core curriculum 2015. Am J Kidney Dis 65:956–966

    Article  PubMed  Google Scholar 

  • Hsing CH, Lin CF, So E, Sun DP, Chen TC, Li CF, Yeh CH (2012) α2-Adrenoceptor agonist dexmedetomidine protects septic acute kidney injury through increasing BMP-7 and inhibiting HDAC2 and HDAC5. Am J Physiol Renal Physiol 303:F1443–F1453

    Article  CAS  PubMed  Google Scholar 

  • Huang W, Liu H, Zhu S, Woodson M, Liu R, Tilton RG, Miller JD, Zhang W (2017) Sirt6 deficiency results in progression of glomerular injury in the kidney. Aging (Albany NY) 9:1069–1083

    Google Scholar 

  • Igarashi P, Somlo S (2002) Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 13:2384–2398

    Article  CAS  PubMed  Google Scholar 

  • Imai N, Hishikawa K, Marumo T, Hirahashi J, Inowa T, Matsuzaki Y, Okano H, Kitamura T, Salant D, Fujita T (2007) Inhibition of histone deacetylase activates side population cells in kidney and partially reverses chronic renal injury. Stem Cells 25:2469–2475

    Article  CAS  PubMed  Google Scholar 

  • Iso T, Kedes L, Hamamori Y (2003) HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol 194:237–255

    Article  CAS  PubMed  Google Scholar 

  • Isono M, Sato A, Okubo K, Asano T, Asano T (2016) Ritonavir interacts with belinostat to cause endoplasmic reticulum stress and histone acetylation in renal cancer cells. Oncol Res 24:327–335

    Article  PubMed  Google Scholar 

  • Jatiani SS, Baker SJ, Silverman LR, Reddy EP (2010) Jak/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies. Genes Cancer 1:979–993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang BH, Jiang G, Zheng JZ, Lu Z, Hunter T, Vogt PK (2001) Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ 12:363–369

    CAS  PubMed  Google Scholar 

  • Jones J, Juengel E, Mickuckyte A, Hudak L, Wedel S, Jonas D, Blaheta RA (2009) The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo. J Cell Mol Med 13:2376–2385

    Article  PubMed  Google Scholar 

  • Juengel E, Engler J, Mickuckyte A, Jones J, Hudak L, Jonas D, Blaheta RA (2010) Effects of combined valproic acid and the epidermal growth factor/vascular endothelial growth factor receptor tyrosine kinase inhibitor AEE788 on renal cell carcinoma cell lines in vitro. BJU Int 105:549–557

    Article  CAS  PubMed  Google Scholar 

  • Juengel E, Dauselt A, Makarević J, Wiesner C, Tsaur I, Bartsch G, Haferkamp A, Blaheta RA (2012) Acetylation of histone H3 prevents resistance development caused by chronic mTOR inhibition in renal cell carcinoma cells. Cancer Lett 324:83–90

    Article  CAS  PubMed  Google Scholar 

  • Juengel E, Makarević J, Tsaur I, Bartsch G, Nelson K, Haferkamp A, Blaheta RA (2013) Resistance after chronic application of the HDAC-inhibitor valproic acid is associated with elevated Akt activation in renal cell carcinoma in vivo. PLoS ONE 8:e53100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang SW, Lee SM, Kim JY, Kim SY, Kim YH, Kim TH, Kang MS, Jang WH, Seo SK (2017) Therapeutic activity of the histone deacetylase inhibitor SB939 on renal fibrosis. Int Immunopharmacol 42:25–31

    Article  CAS  PubMed  Google Scholar 

  • Katayama H, Sasai K, Kawai H, Yuan ZM, Bondaruk J, Suzuki F, Fujii S, Arlinghaus RB, Czerniak BA, Sen S (2004) Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 36:55–62

    Article  CAS  PubMed  Google Scholar 

  • Khan S, Jena G (2014) Sodium butyrate, a HDAC inhibitor ameliorates eNOS, iNOS and TGF-β1-induced fibrogenesis, apoptosis and DNA damage in the kidney of juvenile diabetic rats. Food Chem Toxicol 73:127–139

    Article  CAS  PubMed  Google Scholar 

  • Khan S, Jena G, Tikoo K, Kumar V (2015a) Valproate attenuates the proteinuria, podocyte and renal injury by facilitating autophagy and inactivation of NF-κB/iNOS signaling in diabetic rat. Biochimie 110:1–16

    Article  CAS  PubMed  Google Scholar 

  • Khan S, Jena G, Tikoo K (2015b) Sodium valproate ameliorates diabetes-induced fibrosis and renal damage by the inhibition of histone deacetylases in diabetic rat. Exp Mol Pathol 98:230–239

    Article  CAS  PubMed  Google Scholar 

  • Kim MK, Kang YJ, Kim DH, Hossain MA, Jang JY, Lee SH, Yoon JH, Chun P, Moon HR, Kim HS, Chung HY, Kim ND (2014) A novel hydroxamic acid derivative, MHY218, induces apoptosis and cell cycle arrest through downregulation of NF-κB in HCT116 human colon cancer cells. Int J Oncol 44:256–264

    Article  CAS  PubMed  Google Scholar 

  • Kim MJ, Kim DE, Jeong IG, Choi J, Jang S, Lee JH, Ro S, Hwang JJ, Kim CS (2012) HDAC inhibitors synergize antiproliferative effect of sorafenib in renal cell carcinoma cells. Anticancer Res 32:3161–3168

    CAS  PubMed  Google Scholar 

  • Kinugasa F, Nagatomi I, Nakanishi T, Noto T, Mori H, Matsuoka H, Sudo Y, Mutoh S (2009) Effect of the immunosuppressant histone deacetylase inhibitor FR276457 in a canine renal transplant model. Transpl Immunol 21:198–202

    Article  CAS  PubMed  Google Scholar 

  • Kinugasa F, Noto T, Matsuoka H, Urano Y, Sudo Y, Takakura S, Mutoh S (2010) Prevention of renal interstitial fibrosis via histone deacetylase inhibition in rats with unilateral ureteral obstruction. Transpl Immunol 23:18–23

    Article  CAS  PubMed  Google Scholar 

  • Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW (2002) Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285:1–24

    Article  CAS  PubMed  Google Scholar 

  • Klotz LO, Sánchez-Ramos C, Prieto-Arroyo I, Urbánek P, Steinbrenner H, Monsalve M (2015) Redox regulation of FoxO transcription factors. Redox Biol 6:51–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi T, Terada Y, Kuwana H, Tanaka H, Okado T, Kuwahara M, Tohda S, Sakano S, Sasaki S (2008) Expression and function of the Delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury. Kidney Int 73:1240–1250

    Article  CAS  PubMed  Google Scholar 

  • Komiya Y, Habas R (2008) Wnt signal transduction pathways. Organogenesis 4:68–75

    Article  PubMed  PubMed Central  Google Scholar 

  • Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV, Yoshida M, Toft DO, Pratt WB, Yao TP (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18:601–607

    Article  CAS  PubMed  Google Scholar 

  • Kumari G, Ulrich T, Krause M, Finkernagel F, Gaubatz S (2014) Induction of p21CIP1 protein and cell cycle arrest after inhibition of Aurora B kinase is attributed to aneuploidy and reactive oxygen species. J Biol Chem 289:16072–16084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isshiki K, Isono M, Uzu T, Guarente L, Kashiwagi A, Koya D (2007) SIRT1 inhibits transforming growth factor beta-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation. J Biol Chem 282:151–158

    Article  CAS  PubMed  Google Scholar 

  • Kwon HK, Ahn SH, Park SH, Park JH, Park JW, Kim HM, Park SK, Lee K, Lee CW, Choi E, Han G, Han JW (2009) A novel gamma-lactam-based histone deacetylase inhibitor potently inhibits the growth of human breast and renal cancer cells. Biol Pharm Bull 32:1723–1727

    Article  CAS  PubMed  Google Scholar 

  • Lan A, Du J (2015) Potential role of Akt signaling in chronic kidney disease. Nephrol Dial Transplant 30:385–394

    Article  CAS  PubMed  Google Scholar 

  • Land SC, Tee AR (2007) Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif. J Biol Chem 282:20534–20543

    Article  CAS  PubMed  Google Scholar 

  • Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149:274–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee SY, Kim SI, Choi ME (2015) Therapeutic targets for treating fibrotic kidney diseases. Transl Res 165:512–530

    Article  CAS  PubMed  Google Scholar 

  • Levine MH, Wang Z, Bhatti TR, Wang Y, Aufhauser DD, McNeal S, Liu Y, Cheraghlou S, Han R, Wang L, Hancock WW (2015) Class-specific histone/protein deacetylase inhibition protects against renal ischemia reperfusion injury and fibrosis formation. Am J Transplant 15:965–973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levine MH, Wang Z, Xiao H, Jiao J, Wang L, Bhatti TR, Hancock WW, Beier UH (2016) Targeting Sirtuin-1 prolongs murine renal allograft survival and function. Kidney Int 89:1016–1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin CL, Lee PH, Hsu YC, Lei CC, Ko JY, Chuang PC, Huang YT, Wang SY, Wu SL, Chen YS, Chiang WC, Reiser J, Wang FS (2014) MicroRNA-29a promotion of nephrin acetylation ameliorates hyperglycemia-induced podocyte dysfunction. J Am Soc Nephrol 25:1698–1709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Q, Kaneko S, Yang L, Feldman RI, Nicosia SV, Chen J, Cheng JQ (2004) Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem 279:52175–52182

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Peng L, Seto E, Huang S, Qiu Y (2012a) Modulation of histone deacetylase 6 (HDAC6) nuclear import and tubulin deacetylase activity through acetylation. J Biol Chem 287:29168–29174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu N, Guo JK, Pang M, Tolbert E, Ponnusamy M, Gong R, Bayliss G, Dworkin LD, Yan H, Zhuang S (2012b) Genetic or pharmacologic blockade of EGFR inhibits renal fibrosis. J Am Soc Nephrol 23:854–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu N, He S, Ma L, Ponnusamy M, Tang J, Tolbert E, Bayliss G, Zhao TC, Yan H, Zhuang S (2013) Blocking the class I histone deacetylase ameliorates renal fibrosis and inhibits renal fibroblast activation via modulating TGF-beta and EGFR signaling. PLoS ONE 8:e54001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu R, Zhong Y, Li X, Chen H, Jim B, Zhou MM, Chuang PY, He JC (2014) Role of transcription factor acetylation in diabetic kidney disease. Diabetes 63:2440–2453

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu M, Ning X, Li R, Yang Z, Yang X, Sun S, Qian Q (2017) Signalling pathways involved in hypoxia-induced renal fibrosis. J Cell Mol Med 21:1248–1259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loeffler I, Wolf G (2014) Transforming growth factor-β and the progression of renal disease. Nephrol Dial Transplant 29(Suppl 1):i37–i45

    Article  CAS  PubMed  Google Scholar 

  • Lu TC, Wang ZH, Feng X, Chuang PY, Fang W, Shen Y, Levy DE, Xiong H, Chen N, He JC (2009) Knockdown of Stat3 activity in vivo prevents diabetic glomerulopathy. Kidney Int 76:63–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma T, Huang C, Xu Q, Yang Y, Liu Y, Meng X, Li J, Ye M, Liang H (2017) Suppression of BMP-7 by histone deacetylase 2 promoted apoptosis of renal tubular epithelial cells in acute kidney injury. Cell Death Dis 8:e3139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahalingam D, Medina EC, Esquivel JA 2nd, Espitia CM, Smith S, Oberheu K, Swords R, Kelly KR, Mita MM, Mita AC, Carew JS, Giles FJ, Nawrocki ST (2010) Vorinostat enhances the activity of temsirolimus in renal cell carcinoma through suppression of survivin levels. Clin Cancer Res 16:141–153

    Article  CAS  PubMed  Google Scholar 

  • Manson SR, Song JB, Hruska KA, Austin PF (2014) HDAC dependent transcriptional repression of Bmp-7 potentiates TGF-β mediated renal fibrosis in obstructive uropathy. J Urol 191:242–252

    Article  CAS  PubMed  Google Scholar 

  • Marumo T, Hishikawa K, Yoshikawa M, Hirahashi J, Kawachi S, Fujita T (2010) Histone deacetylase modulates the proinflammatory and -fibrotic changes in tubulointerstitial injury. Am J Physiol Renal Physiol 298:F133–141

    Article  CAS  PubMed  Google Scholar 

  • Meng XM, Nikolic-Paterson DJ, Lan HY (2016) TGF-β: the master regulator of fibrosis. Nat Rev Nephrol 12:325–338

    Article  CAS  PubMed  Google Scholar 

  • Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I (2005) Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 16:4623–4635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mimnaugh EG, Xu W, Vos M, Yuan X, Isaacs JS, Bisht KS, Gius D, Neckers L (2004) Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity. Mol Cancer Ther 3:551–566

    Article  CAS  PubMed  Google Scholar 

  • Mishra N, Reilly CM, Brown DR, Ruiz P, Gilkeson GS (2003) Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse. J Clin Invest 111:539–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mita AC, Mita MM, Nawrocki ST, Giles FJ (2008) Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clin Cancer Res 14:5000–5005

    Article  CAS  PubMed  Google Scholar 

  • Naesens M, Kuypers DR, Sarwal M (2009) Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 4:481–508

    CAS  PubMed  Google Scholar 

  • Nguyễn-Thanh T, Kim D, Lee S, Kim W, Park SK, Kang KP (2017) Inhibition of histone deacetylase 1 ameliorates renal tubulointerstitial fibrosis via modulation of inflammation and extracellular matrix gene transcription in mice. Int J Mol Med. https://doi.org/10.3892/ijmm.2017.3218

    PubMed  PubMed Central  Google Scholar 

  • Noh H, Oh EY, Seo JY, Yu MR, Kim YO, Ha H, Lee HB (2009) Histone deacetylase-2 is a key regulator of diabetes- and transforming growth factor-beta1-induced renal injury. Am J Physiol Renal Physiol 297:F729–F739

    Article  CAS  PubMed  Google Scholar 

  • Okado T, Terada Y, Tanaka H, Inoshita S, Nakao A, Sasaki S (2002) Smad7 mediates transforming growth factor-b-induced apoptosis in mesangial cells. Kidney Int 62:1178–1186

    Article  CAS  PubMed  Google Scholar 

  • Overstreet JM, Samarakoon R, Meldrum KK, Higgins PJ (2014) Redox control of p53 in the transcriptional regulation of TGF-β1 target genes through SMAD cooperativity. Cell Signal 26:1427–1436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pang M, Kothapally J, Mao H, Tolbert E, Ponnusamy M, Chin YE, Zhuang S (2009) Inhibition of histone deacetylase activity attenuates renal fibroblast activation and interstitial fibrosis in obstructive nephropathy. Am J Physiol Renal Physiol 297:F996–F1005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pang M, Ma L, Liu N, Ponnusamy M, Zhao TC, Yan H, Zhuang S (2011) Histone deacetylase 1/2 mediates proliferation of renal interstitial fibroblasts and expression of cell cycle proteins. J Cell Biochem 112:2138–2148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park MJ, Sohrabji F (2016) The histone deacetylase inhibitor, sodium butyrate, exhibits neuroprotective effects for ischemic stroke in middle-aged female rats. J Neuroinflammation 13:300

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Park JH, Jung Y, Kim TY, Kim SG, Jong HS, Lee JW, Kim DK, Lee JS, Kim NK, Kim TY, Bang YJ (2004) Class I histone deacetylase-selective novel synthetic inhibitors potently inhibit human tumor proliferation. Clin Cancer Res 10:5271–5281

    Article  CAS  PubMed  Google Scholar 

  • Plotnikov A, Zehorai E, Procaccia S, Seger R (2011) The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. Biochim Biophys Acta 1813:1619–1633

    Article  CAS  PubMed  Google Scholar 

  • Ponnusamy M, Zhou X, Yan Y, Tang J, Tolbert E, Zhao TC, Gong R, Zhuang S (2014) Blocking sirtuin 1 and 2 inhibits renal interstitial fibroblast activation and attenuates renal interstitial fibrosis in obstructive nephropathy. J Pharmacol Exp Ther 350:243–256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Qian Y, Feldman E, Pennathur S, Kretzler M, Brosius FC 3rd (2008) From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy. Diabetes 57:1439–1445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ranganathan P, Hamad R, Mohamed R, Jayakumar C, Muthusamy T, Ramesh G (2016) Histone deacetylase–mediated silencing of AMWAP expression contributes to cisplatin nephrotoxicity. Kidney Int 89:317–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raphael I, Nalawade S, Eagar TN, Forsthuber TG (2015) T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74:5–17

    Article  CAS  PubMed  Google Scholar 

  • Regna NL, Chafin CB, Hammond SE, Puthiyaveetil AG, Caudell DL, Reilly CM (2014) Class I and II histone deacetylase inhibition by ITF2357 reduces SLE pathogenesis in vivo. Clin Immunol 151:29–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Regna NL, Vieson MD, Luo XM, Chafin CB, Puthiyaveetil AG, Hammond SE, Caudell DL, Jarpe MB, Reilly CM (2016) Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice. Clin Immunol 162:58–73

    Article  CAS  PubMed  Google Scholar 

  • Ren J, Liao X, Vieson MD, Chen M, Scott R, Kazmierczak J, Luo XM, Reilly CM (2017) Selective HDAC6 inhibition decreases early stage of lupus nephritis by down-regulating both innate and adaptive immune responses. Clin Exp Immunol. https://doi.org/10.1111/cei.13046

    Google Scholar 

  • Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8:519–529

    Article  CAS  PubMed  Google Scholar 

  • Roskoski R Jr (2012) ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res 66:105–143

    Article  CAS  PubMed  Google Scholar 

  • Sah NK, Khan Z, Khan GJ, Bisen PS (2006) Structural, functional and therapeutic biology of survivin. Cancer Lett 244:164–171

    Article  CAS  PubMed  Google Scholar 

  • Samarakoon R, Dobberfuhl AD, Cooley C, Overstreet JM, Patel S, Goldschmeding R, Meldrum KK, Higgins PJ (2013a) Induction of renal fibrotic genes by TGF-β1 requires EGFR activation, p53 and reactive oxygen species. Cell Signal 25:2198–2209

    Article  CAS  PubMed  Google Scholar 

  • Samarakoon R, Overstreet JM, Higgins PJ (2013b) TGF-β signaling in tissue fibrosis: redox controls, target genes and therapeutic opportunities. Cell Signal 25:264–268

    Article  CAS  PubMed  Google Scholar 

  • Sanz AB, Sanchez-Niño MD, Ramos AM, Moreno JA, Santamaria B, Ruiz-Ortega M, Egido J, Ortiz A (2010) NF-kappaB in renal inflammation. J Am Soc Nephrol 21(8):1254–1262

    Article  CAS  PubMed  Google Scholar 

  • Sarkar S, Korolchuk VI, Renna M, Imarisio S, Fleming A, Williams A, Garcia-Arencibia M, Rose C, Luo S, Underwood BR, Kroemer G, O’Kane CJ, Rubinsztein DC (2011) Complex inhibitory effects of nitric oxide on autophagy. Mol Cell 43:19–32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sato A, Asano T, Horiguchi A, Ito K, Sumitomo M, Asano T (2010) Combination of suberoylanilide hydroxamic acid and ritonavir is effective against renal cancer cells. Urology 76:764.e7–764.e13

    Article  Google Scholar 

  • Sato A, Asano T, Horiguchi A, Ito K, Sumitomo M, Asano T (2011) Antitumor effect of suberoylanilide hydroxamic acid and topotecan in renal cancer cells. Oncol Res 19:217–223

    Article  PubMed  CAS  Google Scholar 

  • Sato A, Asano T, Ito K, Sumitomo M, Asano T (2012) Suberoylanilide hydroxamic acid (SAHA) combined with bortezomib inhibits renal cancer growth by enhancing histone acetylation and protein ubiquitination synergistically. BJU Int 109:1258–1268

    Article  CAS  PubMed  Google Scholar 

  • Sato A, Asano T, Isono M, Ito K, Asano T (2014) Panobinostat synergizes with bortezomib to induce endoplasmic reticulum stress and ubiquitinated protein accumulation in renal cancer cells. BMC Urol 14:71

    Article  PubMed  PubMed Central  Google Scholar 

  • Senturk E, Manfredi JJ (2013) p53 and cell cycle effects after DNA damage. Methods Mol Biol 962:49–61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sharma S, Sirin Y, Susztak K (2011) The story of Notch and chronic kidney disease. Curr Opin Nephrol Hypertens 20:56–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi Y, Jia B, Xu W, Li W, Liu T, Liu P, Zhao W, Zhang H, Sun X, Yang H, Zhang X, Jin J, Jin Z, Li Z, Qiu L, Dong M, Huang X, Luo Y, Wang X, Wang X, Wu J, Xu J, Yi P, Zhou J, He H, Liu L, Shen J, Tang X, Wang J, Yang J, Zeng Q, Zhang Z, Cai Z, Chen X, Ding K, Hou M, Huang H, Li X, Liang R, Liu Q, Song Y, Su H, Gao Y, Liu L, Luo J, Su L, Sun Z, Tan H, Wang H, Wang J, Wang S, Zhang H, Zhang X, Zhou D, Bai O, Wu G, Zhang L, Zhang Y (2017a) Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China. J Hematol Oncol. 10:69

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi Y, Xu L, Tang J, Fang L, Ma S, Ma X, Nie J, Pi X, Qiu A, Zhuang S, Liu N (2017b) Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury. Am J Physiol Renal Physiol 312:F502–F515

    Article  CAS  PubMed  Google Scholar 

  • Singh BN, Zhang G, Hwa YL, Li J, Dowdy SC, Jiang SW (2010) Nonhistone protein acetylation as cancer therapy targets. Expert Rev Anticancer Ther 10:935–954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stadler WM, Margolin K, Ferber S, McCulloch W, Thompson JA (2006) A phase II study of depsipeptide in refractory metastatic renal cell cancer. Clin Genitourin Cancer. 5:57–60

    Article  CAS  PubMed  Google Scholar 

  • Sureshbabu A, Muhsin SA, Choi ME (2016) TGF-β signaling in the kidney: profibrotic and protective effects. Am J Physiol Renal Physiol 310:F596–F606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talks KL, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL (2000) The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol 157:411–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang Q, Bluestone JA (2013) Regulatory T-cell therapy in transplantation: moving to the clinic. Cold Spring Harb Perspect Med. 3:a015552

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tang XH, Gudas LJ (2011) Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol 6:345–364

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Liu N, Zhuang S (2013) Role of epidermal growth factor receptor in acute and chronic kidney injury. Kidney Int 83:804–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang J, Yan Y, Zhao TC, Gong R, Bayliss G, Yan H, Zhuang S (2014) Class I HDAC activity is required for renal protection and regeneration after acute kidney injury. Am J Physiol Renal Physiol 307:F303–F316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Touma SE, Goldberg JS, Moench P, Guo X, Tickoo SK, Gudas LJ, Nanus DM (2005) Retinoic acid and the histone deacetylase inhibitor trichostatin a inhibit the proliferation of human renal cell carcinoma in a xenograft tumor model. Clin Cancer Res 11:3558–3566

    Article  CAS  PubMed  Google Scholar 

  • Tung CW, Hsu YC, Cai CJ, Shih YH, Wang CJ, Chang PJ, Lin CL (2017) Trichostatin A ameliorates renal tubulointerstitial fibrosis through modulation of the JNK-dependent Notch-2 signaling pathway. Sci Rep 7:14495

    Article  PubMed  PubMed Central  Google Scholar 

  • Turner MD, Nedjai B, Hurst T (2014) Pennington DJ (2014) Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta 1843(11):2563–2582

    Article  CAS  PubMed  Google Scholar 

  • Van Beneden K, Geers C, Pauwels M, Mannaerts I, Wissing KM, Van den Branden C, van Grunsven LA (2013) Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis. Toxicol Appl Pharmacol 271:276–284

    Article  PubMed  CAS  Google Scholar 

  • Veerasamy M, Phanish M, Dockrell ME (2013) Smad mediated regulation of inhibitor of DNA binding 2 and its role in phenotypic maintenance of human renal proximal tubule epithelial cells. PLoS ONE 8:e51842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verheul HM, Salumbides B, Van Erp K, Hammers H, Qian DZ, Sanni T, Atadja P, Pili R (2008) Combination strategy targeting the hypoxia inducible factor-1 alpha with mammalian target of rapamycin and histone deacetylase inhibitors. Clin Cancer Res 14:3589–3597

    Article  CAS  PubMed  Google Scholar 

  • Walsh DW, Roxburgh SA, McGettigan P, Berthier CC, Higgins DG, Kretzler M, Cohen CD, Mezzano S, Brazil DP, Martin F (2008) Co-regulation of Gremlin and Notch signalling in diabetic nephropathy. Biochim Biophys Acta 1782:10–21

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Koka V, Lan HY (2005a) Transforming growth factor-beta and Smad signalling in kidney diseases. Nephrology (Carlton) 10:48–56

    Article  Google Scholar 

  • Wang XF, Qian DZ, Ren M, Kato Y, Wei Y, Zhang L, Fansler Z, Clark D, Nakanishi O, Pili R (2005b) Epigenetic modulation of retinoic acid receptor beta2 by the histone deacetylase inhibitor MS-275 in human renal cell carcinoma. Clin Cancer Res 11:3535–3542

    Article  CAS  PubMed  Google Scholar 

  • Wang S, de Caestecker M, Kopp J, Mitu G, Lapage J, Hirschberg R (2006) Renal bone morphogenetic protein-7 protects against diabetic nephropathy. J Am Soc Nephrol 17:2504–2512

    Article  CAS  PubMed  Google Scholar 

  • Wang RN, Green J, Wang Z, Deng Y, Qiao M, Peabody M, Zhang Q, Ye J, Yan Z, Denduluri S, Idowu O, Li M, Shen C, Hu A, Haydon RC, Kang R, Mok J, Lee MJ, Luu HL, Shi LL (2014a) Bone morphogenetic protein (BMP) signaling in development and human diseases. Genes Dis 1:87–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Liu J, Zhen J, Zhang C, Wan Q, Liu G, Wei X, Zhang Y, Wang Z, Han H, Xu H, Bao C, Song Z, Zhang X, Li N, Yi F (2014b) Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy. Kidney Int 86:712–725

    Article  CAS  PubMed  Google Scholar 

  • Wang YQ, Cao Q, Wang F, Huang LY, Sang TT, Liu F, Chen SY (2015) SIRT1 protects against oxidative stress-induced endothelial progenitor cells apoptosis by inhibiting FOXO3a via FOXO3a ubiquitination and degradation. J Cell Physiol 230:2098–2107

    Article  CAS  PubMed  Google Scholar 

  • Wei Y, Sinha S, Levine B (2008) Dual role of JNK1-mediated phosphorylation of Bcl-2 in autophagy and apoptosis regulation. Autophagy 4:949–951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S (2006) Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 5:835–844

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Huang YF, Zhou XK, Zhang W, Lian YF, Lv XB, Gao XR, Lin HK, Zeng YX, Huang JQ (2015) Skp2 is required for Aurora B activation in cell mitosis and spindle checkpoint. Cell Cycle 14:3877–3884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu WP, Tsai YG, Lin TY, Wu MJ, Lin CY (2017) The attenuation of renal fibrosis by histone deacetylase inhibitors is associated with the plasticity of FOXP3 + IL-17 + T cells. BMC Nephrol 18:225

    Article  PubMed  PubMed Central  Google Scholar 

  • Xia S, Li X, Johnson T, Seidel C, Wallace DP, Li R (2010) Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development 137:1075–1084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu S, Gao Y, Zhang Q, Wei S, Chen Z, Dai X, Zeng Z, Zhao KS (2016) SIRT1/3 activation by resveratrol attenuates acute kidney injury in a septic rat model. Oxid Med Cell Longev 2016:7296092

    PubMed  PubMed Central  Google Scholar 

  • Yanda MK, Liu Q, Cebotaru L (2017a) An inhibitor of histone deacetylase 6 activity, ACY-1215, reduces cAMP and cyst growth in polycystic kidney disease. Am J Physiol Renal Physiol 313:F997–F1004

    Article  PubMed  Google Scholar 

  • Yanda MK, Liu Q, Cebotaru V, Guggino WB, Cebotaru L (2017b) Histone deacetylase 6 inhibition reduces cysts by decreasing cAMP and Ca2+ in knock-out mouse models of polycystic kidney disease. J Biol Chem 292:17897–17908

    Article  CAS  PubMed  Google Scholar 

  • Yoshikawa M, Hishikawa K, Marumo T, Fujita T (2007) Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells. J Am Soc Nephrol 18:58–65

    Article  CAS  PubMed  Google Scholar 

  • Yoshikawa M, Hishikawa K, Idei M, Fujita T (2010) Trichostatin a prevents TGF-beta1-induced apoptosis by inhibiting ERK activation in human renal tubular epithelial cells. Eur J Pharmacol 642:28–36

    Article  CAS  PubMed  Google Scholar 

  • Yu Z, Zhang W, Kone BC (2002) Histone deacetylases augment cytokine induction of the iNOS gene. J Am Soc Nephrol 13:2009–2017

    Article  CAS  PubMed  Google Scholar 

  • Yu L, Border WA, Huang Y, Noble NA (2003) TGF-beta isoforms in renal fibrogenesis. Kidney Int 64:844–856

    Article  CAS  PubMed  Google Scholar 

  • Yung S, Cheung KF, Zhang Q, Chan TM (2010) Anti-dsDNA antibodies bind to mesangial annexin II in lupus nephritis. J Am Soc Nephrol 21:1912–1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yung S, Yap DY, Chan TM (2017) Recent advances in the understanding of renal inflammation and fibrosis in lupus nephritis. F1000Res 6:874

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang T, Fields JZ, Opdenaker L, Otevrel T, Masuda E, Palazzo JP, Isenberg GA, Goldstein SD, Brand M, Boman BM (2010) Survivin-induced Aurora-B kinase activation: a mechanism by which APC mutations contribute to increased mitoses during colon cancer development. Am J Pathol 177:2816–2826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou X, Fan LX, Sweeney WE Jr, Denu JM, Avner ED, Li X (2013) Sirtuin 1 inhibition delays cyst formation in autosomal-dominant polycystic kidney disease. J Clin Invest 123:3084–3098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhuang S (2013) Regulation of STAT signaling by acetylation. Cell Signal 25:1924–1931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This work was supported by the 2016 Inje University research grant.

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Chun, P. Therapeutic effects of histone deacetylase inhibitors on kidney disease. Arch. Pharm. Res. 41, 162–183 (2018). https://doi.org/10.1007/s12272-017-0998-7

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