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Fate and plasticity of renin precursors in development and disease

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Abstract

Renin-expressing cells appear early in the embryo and are distributed broadly throughout the body as organogenesis ensues. Their appearance in the metanephric kidney is a relatively late event in comparison with other organs such as the fetal adrenal gland. The functions of renin cells in extra renal tissues remain to be investigated. In the kidney, they participate locally in the assembly and branching of the renal arterial tree and later in the endocrine control of blood pressure and fluid-electrolyte homeostasis. Interestingly, this endocrine function is accomplished by the remarkable plasticity of renin cell descendants along the kidney arterioles and glomeruli which are capable of reacquiring the renin phenotype in response to physiological demands, increasing circulating renin and maintaining homeostasis. Given that renin cells are sensors of the status of the extracellular fluid and perfusion pressure, several signaling mechanisms (β-adrenergic receptors, Notch pathway, gap junctions and the renal baroreceptor) must be coordinated to ensure the maintenance of renin phenotype—and ultimately the availability of renin—during basal conditions and in response to homeostatic threats. Notably, key transcriptional (Creb/CBP/p300, RBP-J) and posttranscriptional (miR-330, miR125b-5p) effectors of those signaling pathways are prominent in the regulation of renin cell identity. The next challenge, it seems, would be to understand how those factors coordinate their efforts to control the endocrine and contractile phenotypes of the myoepithelioid granulated renin-expressing cell.

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References

  1. Sequeira Lopez ML, Pentz ES, Robert B, Abrahamson DR, Gomez RA (2001) Embryonic origin and lineage of juxtaglomerular cells. Am J Physiol Renal Physiol 281:F345–F356

    CAS  PubMed  Google Scholar 

  2. Sequeira Lopez ML, Gomez RA (2011) Development of the renal arterioles. J Am Soc Nephrol 22:2156–2165

    Article  PubMed  Google Scholar 

  3. Nishimura H, Ogawa M, Sawyer WH (1973) Renin-angiotensin system in primitive bony fishes and a holocephalian. Am J Physiol 224:950–956

    CAS  PubMed  Google Scholar 

  4. Taugner R, Hackenthal E (1989) The juxtaglomerular apparatus: structure and function. Springer, Berlin Heidelberg New York, pp 104–126

    Book  Google Scholar 

  5. Gomez RA, Lynch KR, Sturgill BC, Elwood JP, Chevalier RL, Carey RM, Peach MJ (1989) Distribution of renin mRNA and its protein in the developing kidney. Am J Physiol 257:F850–F858

    CAS  PubMed  Google Scholar 

  6. Ice KS, Geary KM, Gomez RA, Johns DW, Peach MJ, Carey RM (1988) Cell and molecular studies of renin secretion. Clin Exp Hypertens A 10:1169–1187

    CAS  PubMed  Google Scholar 

  7. Keeton TK, Campbell WB (1980) The pharmacologic alteration of renin release. Pharmacol Rev 32:81–227

    CAS  PubMed  Google Scholar 

  8. Sequeira Lopez ML, Pentz ES, Nomasa T, Smithies O, Gomez RA (2004) Renin cells are precursors for multiple cell types that switch to the renin phenotype when homeostasis is threatened. Dev Cell 6:719–728

    Article  PubMed  Google Scholar 

  9. Gomez RA, Chevalier RL, Everett AD, Elwood JP, Peach MJ, Lynch KR, Carey RM (1990) Recruitment of renin gene-expressing cells in adult rat kidneys. Am J Physiol 259:F660–F665

    CAS  PubMed  Google Scholar 

  10. Gomez RA, Lynch KR, Chevalier RL, Everett AD, Johns DW, Wilfong N, Peach MJ, Carey RM (1988) Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition. Am J Physiol 254:F900–F906

    CAS  PubMed  Google Scholar 

  11. Gomez RA, Norwood VF (1995) Developmental consequences of the renin–angiotensin system. Am J Kidney Dis 26:409–431

    Article  CAS  PubMed  Google Scholar 

  12. Kim HS, Maeda N, Oh GT, Fernandez LG, Gomez RA, Smithies O (1999) Homeostasis in mice with genetically decreased angiotensinogen is primarily by an increased number of renin-producing cells. J Biol Chem 274:14210–14217

    Article  CAS  PubMed  Google Scholar 

  13. Tufro-McReddie A, Arrizurieta EE, Brocca S, Gomez RA (1992) Dietary protein modulates intrarenal distribution of renin and its mRNA during development. Am J Physiol 263:F427–F435

    CAS  PubMed  Google Scholar 

  14. Tufro-McReddie A, Chevalier RL, Everett AD, Gomez RA (1993) Decreased perfusion pressure modulates renin and ANG II type 1 receptor gene expression in the rat kidney. Am J Physiol 264:R696–R702

    CAS  PubMed  Google Scholar 

  15. Berg AC, Chernavvsky-Sequeira C, Lindsey J, Gomez RA, Sequeira-Lopez MLS (2013) Pericytes synthesize renin. World J Nephrol 2:11–16

    Article  PubMed Central  PubMed  Google Scholar 

  16. Brunskill EW, Sequeira-Lopez ML, Pentz ES, Lin E, Yu J, Aronow BJ, Potter SS, Gomez RA (2011) Genes that confer the identity of the renin cell. J Am Soc Nephrol 22:2213–2225

    Article  CAS  PubMed  Google Scholar 

  17. Song L, Tuan RS (2006) MicroRNAs and cell differentiation in mammalian development. Birth Defects Res C Embryo Today 78:140–149

    Article  CAS  PubMed  Google Scholar 

  18. Stefani G, Slack FJ (2008) Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 9:219–230

    Article  CAS  PubMed  Google Scholar 

  19. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  20. Vo N, Klein ME, Varlamova O, Keller DM, Yamamoto T, Goodman RH, Impey S (2005) A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc Natl Acad Sci USA 102:16426–16431

    Article  CAS  PubMed  Google Scholar 

  21. Medrano S, Monteagudo MC, Sequeira-Lopez MLS, Pentz ES, Gomez RA (2011) Two microRNAs -miR-330 and miR-125b-5p- mark the juxtaglomerular cell and balance its smooth muscle phenotype. Am J Physiol Renal Physiol 302(1):F29–F37

    Article  PubMed  Google Scholar 

  22. Persson PB, Skalweit A, Mrowka R, Thiele BJ (2003) Control of renin synthesis. Am J Physiol Regul Integr Comp Physiol 285:R491–R497

    PubMed  Google Scholar 

  23. Everett AD, Carey RM, Chevalier RL, Peach MJ, Gomez RA (1990) Renin release and gene expression in intact rat kidney microvessels and single cells. J Clin Invest 86:169–175

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Pan L, Black TA, Shi Q, Jones CA, Petrovic N, Loudon J, Kane C, Sigmund CD, Gross KW (2001) Critical roles of a cyclic AMP responsive element and an E-box in regulation of mouse renin gene expression. J Biol Chem 276:45530–45538

    Article  CAS  PubMed  Google Scholar 

  25. Todorov VT, Volkl S, Friedrich J, Kunz-Schughart LA, Hehlgans T, Vermeulen L, Haegeman G, Schmitz ML, Kurtz A (2005) Role of CREB1 and NF{kappa}B-p65 in the down-regulation of renin gene expression by tumor necrosis factor {alpha}. J Biol Chem 280:24356–24362

    Article  CAS  PubMed  Google Scholar 

  26. Klar J, Sandner P, Muller MW, Kurtz A (2002) Cyclic AMP stimulates renin gene transcription in juxtaglomerular cells. Pflugers Arch 444:335–344

    Article  CAS  PubMed  Google Scholar 

  27. Chen L, Kim SM, Oppermann M, Faulhaber-Walter R, Huang Y, Mizel D, Chen M, Lopez ML, Weinstein LS, Gomez RA, Briggs JP, Schnermann J (2007) Regulation of renin in mice with Cre recombinase-mediated deletion of G protein Gsalpha in juxtaglomerular cells. Am J Physiol Renal Physiol 292:F27–F37

    Article  CAS  PubMed  Google Scholar 

  28. Chen L, Faulhaber-Walter R, Wen Y, Huang Y, Mizel D, Chen M, Sequeira Lopez ML, Weinstein LS, Gomez RA, Briggs JP, Schnermann J (2010) Renal failure in mice with Gsalpha deletion in juxtaglomerular cells. Am J Nephrol 32:83–94

    Article  PubMed  Google Scholar 

  29. Castellanos Rivera RM, Monteagudo MC, Pentz ES, Glenn ST, Gross KW, Carretero O, Sequeira-Lopez ML, Gomez RA (2011) Transcriptional regulator RBP-J regulates the number and plasticity of renin cells. Physiol Genomics 43:1021–1028

    Article  PubMed  Google Scholar 

  30. Wagner C, Jobs A, Schweda F, Kurtz L, Kurt B, Lopez ML, Gomez RA, van Veen TA, de WC, Kurtz A (2010) Selective deletion of Connexin 40 in renin-producing cells impairs renal baroreceptor function and is associated with arterial hypertension. Kidney Int 78:762–768

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Takahashi N, Lopez ML, Cowhig JE Jr, Taylor MA, Hatada T, Riggs E, Lee G, Gomez RA, Kim HS, Smithies O (2005) Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type. J Am Soc Nephrol 16:125–132

    Article  PubMed  Google Scholar 

  32. Yanai K, Saito T, Kakinuma Y, Kon Y, Hirota K, Taniguchi-Yanai K, Nishijo N, Shigematsu Y, Horiguchi H, Kasuya Y, Sugiyama F, Yagami K, Murakami K, Fukamizu A (2000) Renin-dependent cardiovascular functions and renin-independent blood–brain barrier functions revealed by renin-deficient mice. J Biol Chem 275:5–8

    Article  CAS  PubMed  Google Scholar 

  33. Kim HS, Krege JH, Kluckman KD, Hagaman JR, Hodgin JB, Best CF, Jennette JC, Coffman TM, Maeda N, Smithies O (1995) Genetic control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci USA 92:2735–2739

    Article  CAS  PubMed  Google Scholar 

  34. Kihara M, Umemura S, Sumida Y, Yokoyama N, Yabana M, Nyui N, Tamura K, Murakami K, Fukamizu A, Ishii M (1998) Genetic deficiency of angiotensinogen produces an impaired urine concentrating ability in mice. Kidney Int 53:548–555

    Article  CAS  PubMed  Google Scholar 

  35. Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan AJ, Fogo A, Inagami T (1995) Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest 96:2947–2954

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Hilgers KF, Reddi V, Krege JH, Smithies O, Gomez RA (1997) Aberrant renal vascular morphology and renin expression in mutant mice lacking angiotensin-converting enzyme. Hypertension 29:216–221

    Article  CAS  PubMed  Google Scholar 

  37. Krege JH, John SW, Langenbach LL, Hodgin JB, Hagaman JR, Bachman ES, Jennette JC, O’Brien DA, Smithies O (1995) Male–female differences in fertility and blood pressure in ACE-deficient mice. Nature 375:146–148

    Article  CAS  PubMed  Google Scholar 

  38. Esther CR Jr, Howard TE, Marino EM, Goddard JM, Capecchi MR, Bernstein KE (1996) Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Investig 74:953–965

    CAS  PubMed  Google Scholar 

  39. Inokuchi S, Kimura K, Sugaya T, Inokuchi K, Murakami K, Sakai T (2001) Hyperplastic vascular smooth muscle cells of the intrarenal arteries in angiotensin II type 1a receptor null mutant mice. Kidney Int 60:722–731

    Article  CAS  PubMed  Google Scholar 

  40. Oliverio MI, Kim HS, Ito M, Le T, Audoly L, Best CF, Hiller S, Kluckman K, Maeda N, Smithies O, Coffman TM (1998) Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. Proc Natl Acad Sci USA 95:15496–15501

    Article  CAS  PubMed  Google Scholar 

  41. Tsuchida S, Matsusaka T, Chen X, Okubo S, Niimura F, Nishimura H, Fogo A, Utsunomiya H, Inagami T, Ichikawa I (1998) Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes. J Clin Invest 101:755–760

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Pentz ES, Moyano MA, Thornhill BA, Sequeira Lopez ML, Gomez RA (2004) Ablation of renin-expressing juxtaglomerular cells results in a distinct kidney phenotype. Am J Physiol Regul Integr Comp Physiol 286:R474–R483

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA

    Brian Belyea, Silvia Medrano, Ellen S. Pentz & Maria Luisa S. Sequeira-Lopez

  2. Department of Pediatrics, University of Virginia School of Medicine, 409 Lane Road, Room 2001, Charlottesville, VA, 22908, USA

    R. Ariel Gomez

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  1. R. Ariel Gomez
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  4. Ellen S. Pentz
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Correspondence to R. Ariel Gomez.

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Gomez, R.A., Belyea, B., Medrano, S. et al. Fate and plasticity of renin precursors in development and disease. Pediatr Nephrol 29, 721–726 (2014). https://doi.org/10.1007/s00467-013-2688-0

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  • DOI: https://doi.org/10.1007/s00467-013-2688-0

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