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Role of aldose reductase in TGF-β1-induced fibronectin synthesis in human mesangial cells

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Abstract

Accumulation of glomerular extracellular matrix (ECM) may result in glomerulosclerosis. Several lines of evidence indicate a key role for transforming growth factor-β1 (TGF-β1) in glomerular ECM synthesis and degradation, such as fibronectin (FN). Aldose reductase (AR) was proven to be one of the TGF-β1 responsive genes in cultured rat mesangial cells using the SSH–PCR method and there were positive correlation between the AR and TGF-β1 in our previous studies. So we assumed that AR could regulate FN synthesis. In this study, we explored the role of AR in FN production and possible mechanism involved. The expression of AR, FN and c-Jun proteins were analyzed by Western blot and the activity of activator protein-1 (AP-1) was assessed by electrophoretic mobility shift assay (EMSA). Our results showed that AR could mediate the TGF-β1-induced FN production, which may associate with AP-1 activation.

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References

  1. Klahr S, Schreiner G, Ichikawa I (1988) The progression of renal disease. N Engl J Med 318(25):1657–1666

    Article  CAS  PubMed  Google Scholar 

  2. Peten EP, Striker LJ (1994) Progression of glomerular disease. J Intern Med 236(3):241–249

    Article  CAS  PubMed  Google Scholar 

  3. Schnaper HW (1995) Balance between matrix synthesis and degradation: a determinant of glomerulosclerosis. Pediatr Nephrol 9(1):104–111

    Article  CAS  PubMed  Google Scholar 

  4. Baricos WH, Reed JC, Cortez SL (2003) Extracellular matrix degradation by cultured mesangial cells: mediators and modulators. Exp Biol Med (Maywood) 228(9):1018–1022

    CAS  Google Scholar 

  5. Hanahan RAW D (2000) The hallmarks of cancer. Cell 100:57–70

    Article  Google Scholar 

  6. Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC (2003) TGF-beta signal transduction and mesangial cell fibrogenesis. Am J Physiol Renal Physiol 284(2):F243–F252

    CAS  PubMed  Google Scholar 

  7. Yoshioka K, Takemura T, Murakami K, Okada M, Hino S, Miyamoto H, Maki S (1993) Transforming growth factor-beta protein and mRNA in glomeruli in normal and diseased human kidneys. Lab Invest 68(2):154–163

    CAS  PubMed  Google Scholar 

  8. Mozes MM, Bottinger EP, Jacot TA, Kopp JB (1999) Renal expression of fibrotic matrix proteins and of transforming growth factor-beta (TGF-beta) isoforms in TGF-beta transgenic mice. J Am Soc Nephrol 10(2):271–280

    CAS  PubMed  Google Scholar 

  9. Isaka Y, Fujiwara Y, Ueda N, Kaneda Y, Kamada T, Imai E (1993) Glomerulosclerosis induced by in vivo transfection of transforming growth fator-beta or platelet-derived growth factor gene into the rat kidney. J Clin Invest 92(6):2597–2601

    Article  CAS  PubMed  Google Scholar 

  10. Kopp JB, Factor VM, Mozes M, Nagy P, Sanderson N, Bottinger EP, Klotman PE, Thorgeirsson SS (1996) Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive disease. Lab Invest 74(6):991–1003

    CAS  PubMed  Google Scholar 

  11. Imai E, Isaka Y, Akagi Y, Arai M, Moriyama T, Takenaka M, Kaneko T, Horio M, Ando A, Orita Y, Kaneda Y, Ueda N, Kamada T (1996) Application of antisense oligodeoxynucleotides (ODNs) for the intervention of kidney disease. Antisense ODNs for transforming growth factor-beta-suppressed glomerulosclerosis in experimental glomerulonephritis. Contrib Nephrol 118:86–93

    CAS  PubMed  Google Scholar 

  12. LaMendola SCAJ (1989) Cloning and sequence determination of human placental aldose. J Biol Chem 264(25):14775–14777

    PubMed  Google Scholar 

  13. Yabe-Nishimura C (1998) Aldose reductase in glucose toxicity: a potential target for the prevention of diabetic complications. Pharmacol Rev 50(1):21–33

    CAS  PubMed  Google Scholar 

  14. Chandra D, Ramana KV, Friedrich B, Srivastava S, Bhatnagar A, Srivastava SK (2003) Role of aldose reductase in TNF-alpha-induced apoptosis of vascular endothelial cells. Chem Biol Interact 143:605–612

    Article  PubMed  CAS  Google Scholar 

  15. Lin WS, Zhang N, Zhang XR (2001) Effect of aldose reductase expression by transforming growth factor-β1 on rat mesangial cell. Natl Med J. 81(12):744–747 (in Chinese)

    CAS  Google Scholar 

  16. Jiang T, Yang J, Li H (2005) Effect of transforming growth factor-β1 on aldose reductase expression in rat mesangial cells and anti-Thy1 glomerulonephritis. Chinese J Clin. 21:91–94 (in Chinese)

    Google Scholar 

  17. Mao Yong, Schwarzbauer JE (2005) Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol 24:389–399

    Article  CAS  PubMed  Google Scholar 

  18. Komblihtt AR, Pesce CG, Alonso CR, Cramer P, Srebrow A, Werbajh S, Moro AF (1996) The fibronectin gene as a model for splicing and transcription studies. FASEB J 10(2):248–257

    Google Scholar 

  19. Brenmoehi J, Miller SN, Hofmann C, Vogl D, FalK W, Scholmench J, Rogler G (2007) Transforming growth factor-beta 1 induces intestinal myofibroblasts differentiation and modulates their migration. World J Gastroenterol 15(12):1431–1442

    Article  CAS  Google Scholar 

  20. Ziegler D (2008) Treatment of diabetic neuropathy and neuropathic pain: how far have we come? Diabetes Care 31(2):S255–S261

    Article  CAS  PubMed  Google Scholar 

  21. Poncelet AC, de Caestecker MP, Schnaper HW (1999) The transforming growth factor-beta/Smad signaling pathway in present and fuctional in human glomerular mesangial cells. Kindey Int. 56(4):1354–1365

    Article  CAS  Google Scholar 

  22. Jiang T, Che Q, Lin YF, Li H, Zhang N (2006) Aldose Reductase regulates TGF-β1-induced production of fibronectin and type IV collagen in cultured rat mesangial cell. Nephrology 11(2):105–112

    Article  CAS  PubMed  Google Scholar 

  23. Hayashida T, Wu MH, Pierce A, Poncelet AC, Varga J, Schnaper HW (2007) MAP-kinase activity necessary for TGF beta1-stimulated mesangial cell type I collagen expression requires adhesion-dependent phosphorylation of FAK tyrosine 397. J Cell Sci 120(23):4230–4240

    Article  CAS  PubMed  Google Scholar 

  24. Inoki K, Haneda M, Ishida T (2000) Role of mitogen-activated protein kinases as downstream effectors of transforming growth factor beta in mesangial cell. Kidney Int 77:S76–S80

    Article  CAS  Google Scholar 

  25. Hocevar BA, Brown TL, Howe PH (1999) TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. EMBO J 18(5):1345–1356

    Article  CAS  PubMed  Google Scholar 

  26. Angel P, Karin M (1991) The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1072(2–3):129–157

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from National Natural Scientific Foundation of China (NSFC30570857). We also thank Dr John D Hayes, University of Dundee, Scotland for providing AR polyclonal antibody.

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  1. Department of Pathology, Shanghai Medical College, Fudan University, Box 230, 138 Yixueyuan Road, 200032, Shanghai, China

    Yuejuan Zhang, Ping Huang, Tao Jiang, Jingjing Zhao & Nong Zhang

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  1. Yuejuan Zhang
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  2. Ping Huang
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  3. Tao Jiang
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  5. Nong Zhang
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Correspondence to Nong Zhang.

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Zhang, Y., Huang, P., Jiang, T. et al. Role of aldose reductase in TGF-β1-induced fibronectin synthesis in human mesangial cells. Mol Biol Rep 37, 2735–2742 (2010). https://doi.org/10.1007/s11033-009-9811-0

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  • DOI: https://doi.org/10.1007/s11033-009-9811-0

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