Skip to main content
SpringerLink
Log in

Renal Fibrosis

  • Protocol
Fibrosis Research

Part of the book series: Methods in Molecular Medicine ((MIMM,volume 117))

Abstract

The kidney has unique attributes that are related to its complex structure and that affect the nature of fibrogenesis in this organ. It is divided into functional units, called nephrons, that have both a filtering and a reabsorbing component. Sclerosis may initiate in the sites of either of these components but ultimately involves both. The epidemiology and clinical manifestations of renal fibrosis suggest complex genetic and environmental influences on the development of fibrosis. Further, the different structures in the kidney manifest different mechanisms of fibrogenesis. These are determined by a combination of differences in the biology of the affected cells and the physical effects of nephron failure. Although therapy for renal fibrosis remains somewhat problematic, new insights into the mechanisms of the underlying diseases offer the promise of improved approaches to treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. United States Renal Data System (2003) 2003 Annual Data Report. Division of Kidney, Urologic and Hematologic Diseases, NIDDK/NIH, Department of Health and Human Services, Bethesda, MD.

    Google Scholar 

  2. Eddy, A. A. (1994) Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions. J. Am. Soc. Nephrol. 5, 1273–1287.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. Baricos, W. H. (2002) Protease mediated tubular injury: a new direction in acute renal failure? Kidney Int. 61, 1174–1175.

    Article  PubMed  Google Scholar 

  5. Lovett, D. H., Johnson, R. J., Marti, H. P., Martin, J., Davies, M., and Couser, W. G. (1992) Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex-mediated glomerulonephritis. Am. J. Pathol. 141, 85–98.

    PubMed  CAS  Google Scholar 

  6. Schnaper, H. W. (2001) Focal segmental glomerulosclerosis. In: Immunologic Renal Disease, 2nd edition (Neilson, E. G. and Couser, W. G., eds), Lippincott Williams and Willkins, Philadelphia: pp. 1001–1027.

    Google Scholar 

  7. Schnaper, H. W. (2003) Idiopathic focal segmental glomerulosclerosis. Semin. Nephrol. 23, 183–193.

    Article  PubMed  Google Scholar 

  8. Wehrmann, M., Bohle, A., Held, H., Schumm, G., Kendziorra, H., and Pressler, H. (1990) Long-term prognosis of focal sclerosing glomerulonephritis. An analysis of 250 cases with particular regard to tubulointerstitial changes. Clin. Nephrol. 33, 115–122.

    PubMed  CAS  Google Scholar 

  9. Jones, C. L., Buch, S., Post, M., McCulloch, L., Liu, E., and Eddy, A. A. (1991) Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. Kidney Int. 40, 1020–1031.

    Article  PubMed  CAS  Google Scholar 

  10. Mathis, B. J., Kim, S. H., Calabrese, K., Haas, M., Seidman, J. G., Seidman, C. E., and Pollak, M. R. (1998) A locus for inherited focal segmental glomerulosclerosis maps to cromosome 19q13. Kidney Int. 53, 282–286.

    Article  PubMed  CAS  Google Scholar 

  11. Coppes, M. J., Liefers, G. J., Higuchi, M., Zinn, A. B., Balfe, J. W., and Williams, B. R. (1992) Inherited WT1 mutation in Denys-Drash syndrome. Cancer Res. 52, 6125–6128.

    PubMed  CAS  Google Scholar 

  12. Saylam, K. and Simon, P. (2003) WT1 gene mutation responsible for male sex reversal and renal failure: the Frasier syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol. 110, 111–113.

    Article  PubMed  CAS  Google Scholar 

  13. Heathcott, R. W., Morison, I. M., Gubler, M. C., Corbett, R., and Reeve, A. E. (2002) A review of the phenotypic variation due to the Denys-Drash syndromeassociated germline WT1 mutation R362X. Hum. Mutat. 19, 462.

    Article  PubMed  CAS  Google Scholar 

  14. Kestila, M., Lenkkeri, U., Mannikko, M., et al. (1998) Positionally cloned gene for a novel glomerular protein-nephrin-is mutated in congenital nephrotic syndrome. Mol. Cell 1, 575–582.

    Article  PubMed  CAS  Google Scholar 

  15. Boute, N., Gribouval, O., Roselli, S., et al. (2000) NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephritic syndrome. Nat. Genet. 24, 349–354.

    Article  PubMed  CAS  Google Scholar 

  16. Caridi, G., Bertelli, R., Di Duca, M., et al. (2003) Broadening the spectrum of diseases related to podocin mutations. J. Am. Soc. Nephrol. 14, 1278.

    Article  PubMed  CAS  Google Scholar 

  17. Kaplan, J. M., Kim, S.-H., North, K. N., et al. (2000) Mutations in ACTN4, encoding α-actinin-4, cause familial focal segmental glomerulosclerosis. Nat. Genet. 24, 251–256.

    Article  PubMed  CAS  Google Scholar 

  18. Lei, H.-H., Perneger, T. V., Klag, M. J., Whelton, P. K., and Coresh, J. (1998) Familial aggregation of renal disease in a population-based case-control study. J. Am. Soc. Nephrol. 9, 1270–1276.

    PubMed  CAS  Google Scholar 

  19. Freedman, B. I., Isakander, S. S., and Appel, R. G. (1995) The link between hypertension and nephrosis. Am. J. Kidney Dis. 25, 207–221.

    Article  PubMed  CAS  Google Scholar 

  20. Ingulli, E. and Tejani, A. (1991) Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children. Pediatr. Nephrol. 5, 393–397.

    Article  PubMed  CAS  Google Scholar 

  21. Pettitt, D. J., Saad, M. F., Bennett, P. H., Nelson, R. G., and Knowler, W. C. (1990) Familial predisposition to renal disease in two generations of Pima Indians with type-2 (non-insulin dependent) diabetes mellitus. Diabetologia 33, 438–443.

    Article  PubMed  CAS  Google Scholar 

  22. Roy, L. P., Vernier, R. L., and Michael, A. F. (1972) Effect of protein-load proteinuria on glomerular polyanion. Proc. Soc. Exp. Biol. Med. 141, 870–874.

    PubMed  CAS  Google Scholar 

  23. Eddy, A. A., Kim, H., Lopez-Guisa, J., Oda, T., and Soloway, P. D. (2000) Interstitial fibrosis in mice with overload proteinuria: deficiency of TIMP-1 is not protective. Kidney Int. 58, 618–628.

    Article  PubMed  CAS  Google Scholar 

  24. Deen, W. M., Maddox, D. A., Robertson, C. R., and Brenner, B. M. (1974) Dynamics of glomerular ultrafiltration in the rat. VII. Response to reduced renal mass. Am. J. Physiol. 227, 556–562.

    PubMed  CAS  Google Scholar 

  25. Lan, H. Y., Mu, W., Tomita, N., et al. (2003) Inhibition of renal fibrosis by gene transfer of inducible Smad7 using ultrasound-microbubble system in rat UUO model. J. Am. Soc. Nephrol. 14, 1535–1548.

    Article  PubMed  CAS  Google Scholar 

  26. Nakamura, T., Fukui, M., Ebihara, I., Tomino, Y., and Koide, H. (1994) Low protein diet blunts the rise in glomerular gene expression in focal glomerulosclerosis. Kidney Int. 45, 1593–1605.

    Article  PubMed  CAS  Google Scholar 

  27. Glasser, R. J., Velosa, J. A., and Michael, A. F. (1977) Experimental model of focal sclerosis. I. Relationship to protein excretion in aminonucleoside nephrosis. Lab. Invest. 36, 519–526.

    PubMed  CAS  Google Scholar 

  28. Schulze, M., Pruchno, C. J., Burns, M., Baker, P. J., Johnson, R. J., and Couser, W. G. (1993) Glomerular C3c localization indicates ongoing immune deposit formation and complement activation in experimental glomerulonephritis. Am. J. Pathol. 142, 179–187.

    PubMed  CAS  Google Scholar 

  29. Studer, R. K., Craven, P. A., and DeRubertis, F. R. (1993) Role for protein kinase C in the mediation of increased fibronectin accumulation by mesangial cells grown in high-glucose medium. Diabetes 42, 118–126.

    Article  PubMed  CAS  Google Scholar 

  30. Tolins, J. P., Stone, B. G., and Raij, L. (1992) Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury. Kidney Int. 41, 1254–1261.

    Article  PubMed  CAS  Google Scholar 

  31. Kamanna, V. S. and Kirschenbaum, M. A. (1993) Association between verylow-density lipoprotein and glomerular injury in obese Zucker rats. Am. J. Nephrol. 13, 53–58.

    Article  PubMed  CAS  Google Scholar 

  32. Simons, J. L., Provoost, A. P., Anderson, S., et al. (1993) Pathogenesis of glomerular injury in the fawn-hooded rat: early glomerular capillary hypertension predicts glomerular sclerosis. J. Am. Soc. Nephrol. 3, 1775–1782.

    PubMed  CAS  Google Scholar 

  33. Esposito, C., He, C. J., Striker, G. E., Zalups, R. K., and Striker, L. J. (1999) Nature and severity of the glomerular response to nephron reduction is straindependent in mice. Am. J. Pathol. 154, 891–897.

    Article  PubMed  CAS  Google Scholar 

  34. Kos, C. H., Le, T. C., Sinha, S., et al. (2003) Mice deficient in alpha-actinin-4 have severe glomerular disease. J. Clin. Invest. 111, 1683–1690.

    PubMed  CAS  Google Scholar 

  35. Rantanen, M., Palmen, T., Patari, A., et al. (2002) Nephrin TRAP mice lack slit diaphragms and show fibrotic glomeruli and cystic tubular lesions. J. Am. Soc. Nephrol. 13, 1586–1594.

    Article  PubMed  CAS  Google Scholar 

  36. Shih, N.-Y., Li, J., Karpitskii, V., et al. (1999) Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science 286, 312–315.

    Article  PubMed  CAS  Google Scholar 

  37. Schnaper, H. W. and Kopp, J. B. (2003) Renal fibrosis. Frontiers in Bioscience (online) 8, e68–86.

    Article  CAS  Google Scholar 

  38. Clozel, M., Hess, P., Fischli, W., et al. (1999) Age-dependent hypertension in Mpv17-deficient mice, a transgenic model of glomerulosclerosis and inner ear disease. Exp. Gerontol. 34, 1007–1015.

    Article  PubMed  CAS  Google Scholar 

  39. Ljutic, D. and Kes, P. (2003) The role of arterial hypertension in the progression of non-diabetic glomerular diseases. Nephrol. Dial. Transplant. 18(Suppl 5), v28–30.

    Article  PubMed  Google Scholar 

  40. Velosa, J. A., Torres, V. E., Donadio, J. V., et al. (1985) Treatment of severe nephrotic syndrome with meclofenamate: an uncontrolled pilot study. Mayo Clin. Proc. 60, 586–592.

    PubMed  CAS  Google Scholar 

  41. Robson, A. M., Mor, J., Root, E. R., et al. (1979) Mechanism of proteinuria in nonglomerular renal disease. Kidney Int. 16, 416–429.

    Article  PubMed  CAS  Google Scholar 

  42. Narkun-Burgess, D. M., Nolan, C. R., Norman, J. E., et al. (1993) Forty-five year follow-up after uninephrectomy. Kidney Int. 43, 1110–1115.

    Article  PubMed  CAS  Google Scholar 

  43. Yoshida, Y., Fogo, A., and Ichikawa, I. (1989) Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis. Kidney Int. 35, 654–660.

    Article  PubMed  CAS  Google Scholar 

  44. Fogo, A., Hawkins, E. P., Berry, P. L., et al. (1990) Glomerular hypertrophy in minimal change disease predicts subsequent progression to focal glomerular sclerosis. Kidney Int. 38, 115–123.

    Article  PubMed  CAS  Google Scholar 

  45. Kees-Folts, D., Sadow, J. L., and Schreiner, G. F. (1994) Tubular catabolism of albumin is associated with the release of an inflammatory lipid. Kidney Int. 45, 1697–1709.

    Article  PubMed  CAS  Google Scholar 

  46. Kriz, W., Hosser, H., Hahnel, B., Simons, J. L., and Provoost, A. P. (1998) Development of vascular pole-associated glomerulosclerosis in the Fawn-hooded rat. J. Am. Soc. Nephrol. 9, 381–396.

    PubMed  CAS  Google Scholar 

  47. Doublier, S., Seurin, D., Fouqueray, B., et al. (2000) Glomerulosclerosis in mice transgenic for human insulin-like growth factor-binding protein-1. Kidney Int. 57, 2299–2307.

    Article  PubMed  CAS  Google Scholar 

  48. Border, W. A. and Noble, N. A. (1997) TGF-β in kidney fibrosis: a target for gene therapy. Kidney Int. 51, 1388–1396.

    Article  PubMed  CAS  Google Scholar 

  49. Gupta, S., Clarkson, M. R., Duggan, J., and Brady, H. R. (2000) Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibross. Kidney Int. 58, 1389–1399.

    Article  PubMed  CAS  Google Scholar 

  50. Floege, J., Kriz, W., Schulze, M., et al. (1995) Basic fibroblast growth factor augments podocyte injury and induces glomerulosclerosis in rats with experimental membranous nephropathy. J. Clin. Invest. 96, 2809–2819.

    Article  PubMed  CAS  Google Scholar 

  51. Haseley, L. A., Hugo, C., Reidy, M. A., and Johnson, R. J. (1999) Dissociation of mesangial cell migration and proliferation in experimental glomerulonephritis. Kidney Int. 56, 964–972.

    Article  PubMed  CAS  Google Scholar 

  52. Uchiyama-Tanaka, Y., Matsubara, H., Mori, Y., et al. (2002) Involvement of HBEGF and EGF receptor transactivation in TGF-β-mediated fibronectin expression in mesangial cells. Kidney International 62, 799–808.

    Article  PubMed  CAS  Google Scholar 

  53. Iida, H., Seifert, R., Alpers, C. E., et al. (1991) Platet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat. Proc. Natl. Acad. Sci. USA 88, 6560–6564.

    Article  PubMed  CAS  Google Scholar 

  54. Hocher, B., Thone-Reineke, C., Rohmeiss, P., et al. (1997) Endothelin-1 transgenic mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension. J. Clin. Invest. 99, 1380–1389.

    Article  PubMed  CAS  Google Scholar 

  55. Guo, G., Morrissey, J., McCracken, R., Tolley, T., Liapis, H., and Klahr, S. (2001) Contributions of angiotensin II and tumor necrosis factor-alpha to the development of renal fibrosis. Am. J. Physiol. Renal Fluid Elect. 280, F777–F785.

    Google Scholar 

  56. Ophascharoensuk, V., Giachelli, C. M., Gordon, K., et al. (1999) Obstructive uropathy in the mouse: role of osteopontin in interstitial fibrosis and apoptosis. Kidney Int. 56, 571–580.

    Article  PubMed  CAS  Google Scholar 

  57. Wolf, G., Chen, S., Han, D. C., and Ziyadeh, F. N. (2002) Leptin and renal disease. Am. J. Kidney Dis. 39, 1–11.

    Article  PubMed  CAS  Google Scholar 

  58. Yang, J. and Liu, Y. (2002) Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. Am. J. Pathol. 159, 1465–1475.

    Article  Google Scholar 

  59. Patel, K., Harding, P., Haney, L. B., and Glass, W. F., 2nd. (2003) Regulation of the mesangial cell myofibroblast phenotype by actin polymerization. J. Cell Physiol. 195, 435–445.

    Article  PubMed  CAS  Google Scholar 

  60. Hubchak, S. C., Runyan, C. E., Kreisberg, J. I., and Schnaper, H. W. (2003) Cytoskeletal rearrangement and signal transduction in TGF-β1-stimulated mesangial cell collagen accumulation. J. Am. Soc. Nephrol. 14, 1968–1980.

    Article  CAS  Google Scholar 

  61. Hudson, B. G., Kalluri, R., Gunwar, S., et al. (1992) The pathogenesis of Alport syndrome involves type IV collagen molecules containing the alpha 3(IV) chain: evidence from anti-GBM nephritis after renal transplantation. Kidney Int. 42, 179–187.

    Article  PubMed  CAS  Google Scholar 

  62. Hansen, K. M., Berfield, A. K., Spicer, D., and Abrass, C. K. (1998) Rat mesangial cells express two unique isoforms of laminin which modulate mesangial cell phenotype. Matrix Biol. 17, 117–130.

    Article  PubMed  CAS  Google Scholar 

  63. Kalluri, R., Shield, C. F., Todd, P., Hudson, B. G., and Neilson, E. G. (1997) Isoform switching of type IV collagen is developmentally arrested in X-linked Alport syndrome leading to increased susceptibility of renal basement membranes to endoproteolysis. J. Clin. Invest. 99, 2470–2478.

    Article  PubMed  CAS  Google Scholar 

  64. Kashtan, C. E. (1999) Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes. Medicine (Baltimore) 78, 338–360.

    Article  CAS  Google Scholar 

  65. Kikkawa, Y., Virtanen, I., and Miner, J. H. (2003) Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin alpha5 in the glomerular basement membrane. J. Cell Biol. 161, 187–196.

    Article  PubMed  CAS  Google Scholar 

  66. Marti, H.-P., McNeil, L., Davies, M., Martin, J., and Lovett, D. H. (1993) Homology cloning of rat 72 kDa type IV collagenase: cytokine and second messenger inducibility in glomerular mesangial cells. Biochem. J. 291, 441–446.

    PubMed  CAS  Google Scholar 

  67. Carmago, S., Shah, S. V., and Walker, P. D. (2002) Meprin, a brush-border enzyme, plays an important role in hypoxic/ischemic acute renal tubular injury in rats. Kidney Int. 61, 959–966.

    Article  PubMed  CAS  Google Scholar 

  68. Carome, M. A., Striker, L. J., Peten, E. P., et al. (1993) Human glomeruli express TIMP-1 mRNA and TIMP-2 protein and mRNA. Am. J. Physiol. 264, F923–F929.

    Google Scholar 

  69. Tomooka, S., Border, W. A., Marshall, B. C., and Noble, N. A. (1992) Glomerular matrix accumulation is linked to inhibition of the plasmin protease system. Kidney Int. 42, 1462–1469.

    Article  PubMed  CAS  Google Scholar 

  70. Davies, M., Martin, J., Thomas, G. T., and Lovett, D. H. (1992) Proteinases and glomerular matrix turnover. Kidney Int. 41, 671–678.

    Article  PubMed  CAS  Google Scholar 

  71. Eddy, A. A. (2000) Molecular basis of renal fibrosis. Pediatr Nephrol 15, 290–301.

    Article  PubMed  CAS  Google Scholar 

  72. Gaedeke, J., Peters, H., Noble, N. A., and Border, W. A. (2001) Angiotensin II, TGF-β and renal fibrosis. Contrib. Nephrol. 153–160.

    Google Scholar 

  73. Schnaper, H. W., Hayashida, T., Hubchak, S. C., and Poncelet, A.-C. (2003) TGF-β signal transduction and mesangial cell fibrogenesis. Am. J. Physiol. Rena Physiol. 284, F243–F252.

    CAS  Google Scholar 

  74. Hayashida, T., de Caestecker, M. P., and Schnaper, H. W. (2003) Cross-talk between ERK MAP kinase and Smad-signaling pathways enhances TGF-β-dependent responses in human mesangial cells. FASEB J. 17, 1576–1578.

    PubMed  CAS  Google Scholar 

  75. Runyan, C. E., Schnaper, H. W., and Poncelet, A.-C. (2003) Smad3 and PKCδ mediate TGF-β1-induced type I collagen expression in human mesangial cells. Am. J. Physiol. Renal Physiol. 285, F413–F422.

    PubMed  Google Scholar 

  76. Runyan, C. E., Schnaper, H. W., and Poncelet, A.-C. (2004) The phosphatidylinositol 3-kinase Akt pathway enhances Smad3-stimulated mesangial cell collagen I expression in response to TGF-β1. J. Biol. Chem. 279, 2632–2639.

    Article  PubMed  CAS  Google Scholar 

  77. McGowan, T. A., Madesh, M., Zhu, Y., et al. (2002) TGF-b-induced Ca2+ influx involves the type III IP3 receptor and regulates actin cytskeleton. Am. J. Physiol. Renal Physiol. 282, F910–F920.

    PubMed  CAS  Google Scholar 

  78. Poncelet, A.-C. and Schnaper, H. W. (2001) Sp1 and Smad proteins cooperate to mediate TGF-β1-induced α2(I) collagen expression in human glomerular mesangial cells. J. Biol. Chem. 276, 6983–6992.

    Article  PubMed  CAS  Google Scholar 

  79. Cheng, J. and Grande, J. P. (2002) Transforming growth factor-β signal transduction and progressive renal disease. Exp. Biol. Med. (Maywood) 227, 943–956.

    CAS  Google Scholar 

  80. Kawata, Y., Suzuki, H., Higaki, Y., et al. (2002) bcn-1 element-dependent activation of the laminin γ1 chain gene by the cooperative action of transcription factor E2 (TFE3) and Smad proteins. J. Biol. Chem. 277, 11,375–11,384.

    Article  PubMed  CAS  Google Scholar 

  81. Higaki, Y., Schullery, D., Kawata, Y., Shnyreva, M., Abrass, C. K., and Bomsztyk, K. (2002) Synergistic activation of the rat laminin γ1 chain promoter by the gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1. Nucl. Acids Res. 30, 2270–2279.

    Article  PubMed  CAS  Google Scholar 

  82. Yang, J., Dai, C., and Liu, Y. (2003) Hepatocyte growth factor suppresses renal interstitial myofibroblast activation and intercepts Smad signal transduction. Am. J. Pathol. 163, 621–632.

    Article  PubMed  CAS  Google Scholar 

  83. Yang, J. and Liu, Y. (2002) Blockage of tubular epithelial to myofibroblast tran sition by hepatcyte growth factor prevents renal interstitial fibrosis. J. Am. Soc. Nephrol. 13, 96–107.

    PubMed  CAS  Google Scholar 

  84. Isono, M., Chen, S., Hong, S. W., Iglesias-de la Cruz, M. C., and Ziyadeh, F. N. (2002) Smad pathway is activated in the diabetic mouse kidney and Smad3 mediates TGF-β-induced fibronectin in mesangial cells. Biochem. Biophys. Res. Commun. 296, 1356–1365.

    Article  PubMed  CAS  Google Scholar 

  85. Fujimoto, M., Maezawa, Y., Yokote, K., et al. (2003) Mice lacking Smad3 are protected against streptozotocin-induced diabetic glomerulopathy. Biochem. Biophys. Res. Commun. 305, 1002–1007.

    Article  PubMed  CAS  Google Scholar 

  86. Sato, M., Muragaki, Y., Saika, S., Roberts, A. B., and Ooshima, A. (2003) Targeted disruption of TGF-β1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J. Clin. Invest. 112, 1486–1494.

    PubMed  CAS  Google Scholar 

  87. Wang, X., Shaw, S., Amiri, F., Eaton, D. C., and Marrero, M. B. (2002) Inhibition of the Jak/STAT signaling pathway prevents the high glucose-induced increase in TGF-β and fibronectin synthesis in mesangial cells. Diabetes 51, 3505–3509.

    Article  PubMed  CAS  Google Scholar 

  88. Amiri, F., Shaw, S., Wang, X., Tang, J., Waller, J. L., Eaton, D. C., and Marrero, M. B. (2002) Angiotensin II activation of the JAK/STAT pathway in mesangial cells is altered by high glucose. Kidney Int. 61, 1605–1616.

    Article  PubMed  CAS  Google Scholar 

  89. Bhandari, B. K., Feliers, D., Duraisamy, S., et al. (2001) Insulin regulation of protein translation repressor 4E-BP1, and eIF4E-binding protein, in renal epithelial cells. Kidney Int. 59, 866–875.

    Article  PubMed  CAS  Google Scholar 

  90. Guan, Y. and Breyer, M. D. (2001) Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease. Kidney Int. 60, 14–30.

    Article  PubMed  CAS  Google Scholar 

  91. Routh, R. E., Johnson, J. H., and McCarthy, K. J. (2002) Troglitazone suppresses the secretion of type I collagen by mesangial cells in vitro. Kidney Int. 61, 1365–1376.

    Article  PubMed  CAS  Google Scholar 

  92. Ma, L. J., Marcantoni, C., Linton, M. F., Fazio, S., and Fogo, A. B. (2001) Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects against nondiabetic glomerulosclerosis in rats. Kidney Int. 59, 1899–1910.

    Article  PubMed  CAS  Google Scholar 

  93. Yorgin, P. D., Krasher, J., and Al-Uzri, A. Y. (2001) Pulse methylprednisolone treatment of idiopathic steroid-resistant nephrotic syndrome. Pediatr. Nephrol. 16, 245–250.

    Article  PubMed  CAS  Google Scholar 

  94. Rydel, J. J., Korbet, S. M., Borok, R. Z., and Schwartz, M. M. (1995) Focal segmental glomerulosclerosis in adults: presentation, course and response to treatment. Am. J. Kid. Dis. 25, 534–542.

    Article  PubMed  CAS  Google Scholar 

  95. Ingulli, E., Baqi, N., Ahmad, H., Moazami, S., and Tejani, A. (1995) Aggressive, long-term cyclosporine therapy for steroid-resistant focal segmental glomerulosclerosis. J. Am. Soc. Nephrol. 5, 1820–1825.

    PubMed  CAS  Google Scholar 

  96. Cattran, D. C. and Rao, P. (1998) Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. Am. J. Kidney Dis. 32, 72–79.

    Article  PubMed  CAS  Google Scholar 

  97. Rossing, K., Jacobsen, P., Pietraszek, L., and Parving, H. H. (2003) Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized doubleblind crossover trial. Diabetes Care 26, 2268–2274.

    Article  PubMed  CAS  Google Scholar 

  98. Levey, A. S., Adler, S., Caggiula, A. W., et al. (1996) Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am. J. Kidney Dis. 27, 652–663.

    Article  PubMed  CAS  Google Scholar 

  99. Hansen, H. P., Tauber-Lassen, E., Jensen, B. R., and Parving, H. H. (2002) Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy. Kidney Int. 62, 220–228.

    Article  PubMed  Google Scholar 

  100. Chan, M. K., Kwan, S. Y., Chan, K. W., and Yeung, C. K. (1987) Controlled trial of antiplatelet agents in mesangial IgA glomerulonephritis. Am. J. Kidney Dis. 9, 417–421.

    PubMed  CAS  Google Scholar 

  101. Wolf, G., Ziyadeh, F. N., Zahner, G., and Stahl, R. A. (1995) Angiotensin IIstimulated expression of transforming growth factor b in renal proximal tubular cells: attenuation after stable transfection with the c-mas oncogene. Kidney Int. 48, 1818–1827.

    Article  PubMed  CAS  Google Scholar 

  102. Iyer, S. N., Gurujeyalakshmi, G., and Giri, S. N. (1999) Effects of pirfenidone on transforming growth factor-b gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J. Pharmacol. Exp. Ther. 291, 367–373.

    PubMed  CAS  Google Scholar 

  103. Bobadilla, N. A., Tack, I., Tapia, E., et al. (2001) Pentosan polysulfate prevents glomerular hypertension and structural injury despite persisting hypertension in 5/6 nephrectomy rats. J. Am. Soc. Nephrol. 12, 2080–2087.

    PubMed  CAS  Google Scholar 

  104. Mishra-Gorur, K., Singer, H. A., and Castellot, J. J., Jr. (2002) Heparin inhibits phosphorylation and autonomous activity of Ca(2+)/calmodulin-dependent protein kinase II in vascular smooth muscle cells. Am. J. Pathol. 161, 1893–1901.

    Article  PubMed  CAS  Google Scholar 

  105. Poncelet, A.-C. and Schnaper, H. W. (1998) Regulation of mesangial cell collagen turnover by transforming growth factor-β1. Am. J. Physiol. Renal Physiol 275, F458–F466.

    CAS  Google Scholar 

  106. Ganta, D. R., McCarthy, M. B., and Gronowicz, G. A. (1997) Ascorbic acid alters collagen integrins in bone culture. Endocrinology 138, 3606–3612.

    Article  PubMed  CAS  Google Scholar 

  107. Mott, J. D., Khalifah, R. G., Nagase, H., Shield, C. F., 3rd, Hudson, J. K., and Hudson, B. G. (1997) Nonenzymatic glycation of type IV collagen and matrix metalloproteinase susceptibility. Kidney Int. 52, 1302–1312.

    Article  PubMed  CAS  Google Scholar 

  108. Zeisberg, M., Hanai, J., Sugimoto, H., Mammoto, T., Charytan, D., Strutz, F., and Kalluri, R. (2003) BMP-7 counteracts TGF-β1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat. Med. 9, 964–968.

    Article  PubMed  CAS  Google Scholar 

  109. Shi, Y. and Massague, J. (2003) Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113, 685–700.

    Article  PubMed  CAS  Google Scholar 

  110. Cochrane, A. L. and Ricardo, S. D. (2003) Oxidant stress and regulation of chemokines in the development of renal interstitial fibrosis. Contrib. Nephrol. 139, 102–119s

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Supported in part by Grant R01-DK49362 from the National Institute of Diabetes, Digestive, and Kidney Diseases.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Northwestern University, Children’s Memorial Research Center, Chicago, IL

    H. William Schnaper

Authors
  1. H. William Schnaper
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, Chicago, IL

    John Varga MD

  2. College of Physicians and Surgeons, Columbia University, New York, NY

    David A. Brenner MD

  3. University of Michigan Medical School, Ann Arbor, MI

    Sem H. Phan MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc.

About this protocol

Cite this protocol

Schnaper, H.W. (2005). Renal Fibrosis. In: Varga, J., Brenner, D.A., Phan, S.H. (eds) Fibrosis Research. Methods in Molecular Medicine, vol 117. Humana Press. https://doi.org/10.1385/1-59259-940-0:045

Download citation

  • DOI: https://doi.org/10.1385/1-59259-940-0:045

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-479-1

  • Online ISBN: 978-1-59259-940-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation