Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Renal fibrosis

  • Cho, Min-Hyun (Department of Pediatrics, Kyungpook National University School of Medicine)
  • Received : 2010.05.19
  • Accepted : 2010.06.14
  • Published : 2010.07.15
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Abstract

Renal fibrosis, characterized by tubulointerstitial fibrosis and glomerulosclerosis, is the final manifestation of chronic kidney disease. Renal fibrosis is characterized by an excessive accumulation and deposition of extracellular matrix components. This pathologic result usually originates from both underlying complicated cellular activities such as epithelial-to-mesenchymal transition, fibroblast activation, monocyte/macrophage infiltration, and cellular apoptosis and the activation of signaling molecules such as transforming growth factor beta and angiotensin II. However, because the pathogenesis of renal fibrosis is extremely complicated and our knowledge regarding this condition is still limited, further studies are needed.

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References

  1. Liu Y. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int 2006;69:213-7. https://doi.org/10.1038/sj.ki.5000054
  2. el Nahas AM, Muchaneta-Kubara EC, Essawy M, Soylemezoglu O. Renal fibrosis: insights into pathogenesis and treatment. Int J Biochem Cell Biol 1997;29:55-62. https://doi.org/10.1016/S1357-2725(96)00119-7
  3. Eitner F, Floege J. Novel insights into renal fibrosis. Curr Opin Nephrol Hypertens 2003;12:227-32. https://doi.org/10.1097/00041552-200305000-00002
  4. Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies. N Engl J Med 1998;339:1448-56. https://doi.org/10.1056/NEJM199811123392007
  5. Zeisberg M, Soubasakos MA, Kalluri R. Animal models of renal fibrosis. Methods Mol Med 2005;117:261-72.
  6. Lloyd CM, Minto AW, Dorf ME, Proudfoot A, Wells TN, Salant DJ, et al. RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis. J Exp Med 1997;185:1371-80. https://doi.org/10.1084/jem.185.7.1371
  7. Cosgrove D, Meehan DT, Grunkemeyer JA, Kornak JM, Sayers R, Hunter WJ, et al. Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome. Genes Dev 1996;10:2981-92. https://doi.org/10.1101/gad.10.23.2981
  8. Miner JH, Sanes JR. Molecular and functional defects in kidneys of mice lacking collagen alpha 3(IV): implications for Alport syndrome. J Cell Biol 1996;135:1403-13. https://doi.org/10.1083/jcb.135.5.1403
  9. Hamano Y, Grunkemeyer JA, Sudhakar A, Zeisberg M, Cosgrove D, Morello R, et al. Determinants of vascular permeability in the kidney glomerulus. J Biol Chem 2002;277:31154-62. https://doi.org/10.1074/jbc.M204806200
  10. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 2002;110:341-50. https://doi.org/10.1172/JCI0215518
  11. Guo JK, Menke AL, Gubler MC, Clarke AR, Harrison D, Hammes A, et al. WT1 is a key regulator of podocyte function: reduced expression levels cause crescentic glomerulonephritis and mesangial sclerosis. Hum Mol Genet 2002;11:651-9. https://doi.org/10.1093/hmg/11.6.651
  12. Assmann KJ, van Son JP, Dijkman HB, Mentzel S, Wetzels JF. Antibody-induced albuminuria and accelerated focal glomerulosclerosis in the Thy-1.1 transgenic mouse. Kidney Int 2002;62:116-26. https://doi.org/10.1046/j.1523-1755.2002.00428.x
  13. Thornhill BA, Burt LE, Chen C, Forbes MS, Chevalier RL. Variable chronic partial ureteral obstruction in the neonatal rat: a new model of ureteropelvic junction obstruction. Kidney Int 2005;67:42-52. https://doi.org/10.1111/j.1523-1755.2005.00052.x
  14. Chevalier RL, Thornhill BA, Wolstenholme JT, Kim A. Unilateral ureteral obstruction in early development alters renal growth: dependence on the duration of obstruction. J Urol 1999;161:309-13. https://doi.org/10.1016/S0022-5347(01)62137-2
  15. Eddy AA. Molecular basis of renal fibrosis. Pediatr Nephrol 2000;15:290-301. https://doi.org/10.1007/s004670000461
  16. Wang SN, Lapage J, Hirschberg R. Glomerular ultrafiltration and apical tubular action of IGF-I, TGF-beta, and HGF in nephrotic syndrome. Kidney Int 1999;56:1247-51. https://doi.org/10.1046/j.1523-1755.1999.00698.x
  17. Wang Y, Chen J, Chen L, Tay YC, Rangan GK, Harris DC. Induction of monocyte chemoattractant protein-1 in proximal tubule cells by urinary protein. J Am Soc Nephrol 1997;8:1537-45.
  18. Grandaliano G, Gesualdo L, Ranieri E, Monno R, Montinaro V, Marra F, et al. Monocyte chemotactic peptide-1 expression in acute and chronic human nephritides: a pathogenetic role in interstitial monocytes recruitment. J Am Soc Nephrol 1996;7:906-13.
  19. Lloyd CM, Dorf ME, Proudfoot A, Salant DJ, Gutierrez-Ramos JC. Role of MCP-1 and RANTES in inflammation and progression to fibrosis during murine crescentic nephritis. J Leukoc Biol 1997;62:676-80. https://doi.org/10.1002/jlb.62.5.676
  20. Biancone L, David S, Della Pietra V, Montrucchio G, Cambi V, Camussi G. Alternative pathway activation of complement by cultured human proximal tubular epithelial cells. Kidney Int 1994;45:451-60. https://doi.org/10.1038/ki.1994.59
  21. Tang S, Sheerin NS, Zhou W, Brown Z, Sacks SH. Apical proteins stimulate complement synthesis by cultured human proximal tubular epithelial cells. J Am Soc Nephrol 1999;10:69-76.
  22. Ricardo SD, Levinson ME, DeJoseph MR, Diamond JR. Expression of adhesion molecules in rat renal cortex during experimental hydronephrosis. Kidney Int 1996;50:2002-10. https://doi.org/10.1038/ki.1996.522
  23. Okada H, Moriwaki K, Kalluri R, Takenaka T, Imai H, Ban S, et al. Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats. Am J Physiol Renal Physiol 2000;278:F110-21. https://doi.org/10.1152/ajprenal.2000.278.1.F110
  24. Strutz F, Muller GA. Renal fibrosis and the origin of the renal fibroblast. Nephrol Dial Transplant 2006;21:3368-70. https://doi.org/10.1093/ndt/gfl199
  25. Bottinger EP, Bitzer M. TGF-beta signaling in renal disease. J Am Soc Nephrol 2002;13:2600-10. https://doi.org/10.1097/01.ASN.0000033611.79556.AE
  26. Fukasawa H, Yamamoto T, Togawa A, Ohashi N, Fujigaki Y, Oda T, et al. Down-regulation of Smad7 expression by ubiquitin-dependent degradation contributes to renal fibrosis in obstructive nephropathy in mice. Proc Natl Acad Sci U S A 2004;101:8687-92. https://doi.org/10.1073/pnas.0400035101
  27. Kopp JB, Factor VM, Mozes M, Nagy P, Sanderson N, Bottinger EP, et al. Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive renal disease. Lab Invest 1996;74:991-1003.
  28. Schuster N, Krieglstein K. Mechanisms of TGF-beta-mediated apoptosis. Cell Tissue Res 2002;307:1-14. https://doi.org/10.1007/s00441-001-0479-6
  29. Schiffer M, Bitzer M, Roberts IS, Kopp JB, ten Dijke P, Mundel P, et al. Apoptosis in podocytes induced by TGF-beta and Smad7. J Clin Invest 2001;108:807-16. https://doi.org/10.1172/JCI200112367
  30. Oldfield MD, Bach LA, Forbes JM, Nikolic-Paterson D, McRobert A, Thallas V, et al. Advanced glycation end products cause epithelial-myofibroblast transdifferentiation via the receptor for advanced glycation end products (RAGE). J Clin Invest 2001;108:1853-63. https://doi.org/10.1172/JCI11951
  31. Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC. TGF-beta signal transduction and mesangial cell fibrogenesis. Am J Physiol Renal Physiol 2003;284:F243-52. https://doi.org/10.1152/ajpcell.00305.2002
  32. Ma LJ, Jha S, Ling H, Pozzi A, Ledbetter S, Fogo AB. Divergent effects of low versus high dose anti-TGF-beta antibody in puromycin aminonucleoside nephropathy in rats. Kidney Int 2004;65:106-15. https://doi.org/10.1111/j.1523-1755.2004.00381.x
  33. Wang W, Huang XR, Li AG, Liu F, Li JH, Truong LD, et al. Signaling mechanism of TGF-beta1 in prevention of renal inflammation: role of Smad7. J Am Soc Nephrol 2005;16:1371-83. https://doi.org/10.1681/ASN.2004121070
  34. Ruiz-Ortega M, Ruperez M, Esteban V, Rodriguez-Vita J, Sanchez-Lopez E, Carvajal G, et al. Angiotensin II: a key factor in the inflammatory and fibrotic response in kidney diseases. Nephrol Dial Transplant 2006;21:16-20. https://doi.org/10.1093/ndt/gfi265
  35. Yayama K, Okamoto H. Angiotensin II-induced vasodilation via type 2 receptor: role of bradykinin and nitric oxide. Int Immunopharmacol 2008;8:312-8. https://doi.org/10.1016/j.intimp.2007.06.012
  36. Matsubara H. Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases. Circ Res 1998;83:1182-91. https://doi.org/10.1161/01.RES.83.12.1182
  37. Viswanathan M, Tsutsumi K, Correa FM, Saavedra JM. Changes in expression of angiotensin receptor subtypes in the rat aorta during development. Biochem Biophys Res Commun 1991;179:1361-7. https://doi.org/10.1016/0006-291X(91)91723-P
  38. Batenburg WW, Garrelds IM, Bernasconi CC, Juillerat-Jeanneret L, van Kats JP, Saxena PR, et al. Angiotensin II type 2 receptor-mediated vasodilation in human coronary microarteries. Circulation 2004;109:2296-301. https://doi.org/10.1161/01.CIR.0000128696.12245.57
  39. Wenzel UO, Krebs C, Benndorf R. The angiotensin II type 2 receptor in renal disease. J Renin Angiotensin Aldosterone Syst 2010;11:37-41. https://doi.org/10.1177/1470320309347787
  40. Campistol JM, Inigo P, Jimenez W, Lario S, Clesca PH, Oppenheimer F, et al. Losartan decreases plasma levels of TGF-beta1 in transplant patients with chronic allograft nephropathy. Kidney Int 1999;56:714-9. https://doi.org/10.1046/j.1523-1755.1999.00597.x
  41. Warnholtz A, Nickenig G, Schulz E, Macharzina R, Brasen JH, Skatchkov M, et al. Increased NADH-oxidase-mediated superoxide production in the early stages of atherosclerosis: evidence for involvement of the renin-angiotensin system. Circulation 1999;99:2027-33. https://doi.org/10.1161/01.CIR.99.15.2027
  42. Hegarty NJ, Young LS, Kirwan CN, O'Neill AJ, Bouchier-Hayes DM, Sweeney P, et al. Nitric oxide in unilateral ureteral obstruction: effect on regional renal blood flow. Kidney Int 2001;59:1059-65. https://doi.org/10.1046/j.1523-1755.2001.0590031059.x
  43. Chen CO, Park MH, Forbes MS, Thornhill BA, Kiley SC, Yoo KH, et al. Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat. Am J Physiol Renal Physiol 2007;292:F946-55. https://doi.org/10.1152/ajprenal.00287.2006
  44. Perbal B. CCN proteins: multifunctional signalling regulators. Lancet 2004;363:62-4. https://doi.org/10.1016/S0140-6736(03)15172-0
  45. Ito Y, Aten J, Bende RJ, Oemar BS, Rabelink TJ, Weening JJ, et al. Expression of connective tissue growth factor in human renal fibrosis. Kidney Int 1998;53:853-61. https://doi.org/10.1111/j.1523-1755.1998.00820.x
  46. Ruperez M, Lorenzo O, Blanco-Colio LM, Esteban V, Egido J, Ruiz-Ortega M. Connective tissue growth factor is a mediator of angiotensin II-induced fibrosis. Circulation 2003;108:1499-505. https://doi.org/10.1161/01.CIR.0000089129.51288.BA
  47. Esteban V, Lorenzo O, Ruperez M, Suzuki Y, Mezzano S, Blanco J, et al. Angiotensin II, via AT1 and AT2 receptors and NF-kappaB pathway, regulates the inflammatory response in unilateral ureteral obstruction. J Am Soc Nephrol 2004;15:1514-29. https://doi.org/10.1097/01.ASN.0000130564.75008.F5
  48. Lin SL, Chen YM, Chien CT, Chiang WC, Tsai CC, Tsai TJ. Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. J Am Soc Nephrol 2002;13:2916-29. https://doi.org/10.1097/01.ASN.0000034909.10994.8A
  49. Ostendorf T, Kunter U, Grone HJ, Bahlmann F, Kawachi H, Shimizu F, et al. Specific antagonism of PDGF prevents renal scarring in experimental glomerulonephritis. J Am Soc Nephrol 2001;12:909-18.
  50. Eitner F, Ostendorf T, Van Roeyen C, Kitahara M, Li X, Aase K, et al. Expression of a novel PDGF isoform, PDGF-C, in normal and diseased rat kidney. J Am Soc Nephrol 2002;13:910-7.
  51. Changsirikulchai S, Hudkins KL, Goodpaster TA, Volpone J, Topouzis S, Gilbertson DG, et al. Platelet-derived growth factor-D expression in developing and mature human kidneys. Kidney Int 2002;62:2043-54. https://doi.org/10.1046/j.1523-1755.2002.00662.x
  52. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988;332:411-5. https://doi.org/10.1038/332411a0
  53. Hargrove GM, Dufresne J, Whiteside C, Muruve DA, Wong NC. Diabetes mellitus increases endothelin-1 gene transcription in rat kidney. Kidney Int 2000;58:1534-45. https://doi.org/10.1046/j.1523-1755.2000.00315.x
  54. Richter CM. Role of endothelin in chronic renal failure--developments in renal involvement. Rheumatology (Oxford) 2006;45 Suppl 3:Siii36-8.
  55. Sorokin A, Kohan DE. Physiology and pathology of endothelin-1 in renal mesangium. Am J Physiol Renal Physiol 2003;285:F579-89. https://doi.org/10.1152/ajprenal.00019.2003
  56. Kon V, Hunley TE, Fogo A. Combined antagonism of endothelin A/B receptors links endothelin to vasoconstriction whereas angiotensin II effects fibrosis. Studies in chronic cyclosporine nephrotoxicity in rats. Transplantation 1995;60:89-95. https://doi.org/10.1097/00007890-199507150-00017
  57. Guo G, Morrissey J, McCracken R, Tolley T, Klahr S. Role of TNFR1 and TNFR2 receptors in tubulointerstitial fibrosis of obstructive nephropathy. Am J Physiol 1999;277:F766-72. https://doi.org/10.1152/ajpcell.1999.277.4.C766
  58. Lan HY, Nikolic-Paterson DJ, Zarama M, Vannice JL, Atkins RC. Suppression of experimental crescentic glomerulonephritis by the interleukin-1 receptor antagonist. Kidney Int 1993;43:479-85. https://doi.org/10.1038/ki.1993.70
  59. Liu Y. Hepatocyte growth factor and the kidney. Curr Opin Nephrol Hypertens 2002;11:23-30. https://doi.org/10.1097/00041552-200201000-00004
  60. Liu Y. Hepatocyte growth factor in kidney fibrosis: therapeutic potential and mechanisms of action. Am J Physiol Renal Physiol 2004;287:F7-16. https://doi.org/10.1152/ajprenal.00451.2003
  61. Yang J, Liu Y. Delayed administration of hepatocyte growth factor reduces renal fibrosis in obstructive nephropathy. Am J Physiol Renal Physiol 2003;284:F349-57. https://doi.org/10.1152/ajpcell.00066.2002
  62. Mizuno S, Nakamura T. Suppressions of chronic glomerular injuries and TGF-beta 1 production by HGF in attenuation of murine diabetic nephropathy. Am J Physiol Renal Physiol 2004;286:F134-43. https://doi.org/10.1152/ajprenal.00199.2003
  63. Li Y, Yang J, Dai C, Wu C, Liu Y. Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis. J Clin Invest 2003;112:503-16. https://doi.org/10.1172/JCI200317913
  64. Liu Y, Sun AM, Dworkin LD. Hepatocyte growth factor protects renal epithelial cells from apoptotic cell death. Biochem Biophys Res Commun 1998;246:821-6. https://doi.org/10.1006/bbrc.1998.8676
  65. Gong R, Rifai A, Tolbert EM, Centracchio JN, Dworkin LD. Hepatocyte growth factor modulates matrix metalloproteinases and plasminogen activator/plasmin proteolytic pathways in progressive renal interstitial fibrosis. J Am Soc Nephrol 2003;14:3047-60. https://doi.org/10.1097/01.ASN.0000098686.72971.DB
  66. Motazed R, Colville-Nash P, Kwan JT, Dockrell ME. BMP-7 and proximal tubule epithelial cells: activation of multiple signaling pathways reveals a novel anti-fibrotic mechanism. Pharm Res 2008;25:2440-6. https://doi.org/10.1007/s11095-008-9551-1
  67. Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, et al. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 2003;9:964-8. https://doi.org/10.1038/nm888
  68. Wang S, Hirschberg R. BMP7 antagonizes TGF-beta -dependent fibrogenesis in mesangial cells. Am J Physiol Renal Physiol 2003;284:F1006-13. https://doi.org/10.1152/ajpcell.00258.2002
  69. Chevalier RL, Goyal S, Kim A, Chang AY, Landau D, LeRoith D. Renal tubulointerstitial injury from ureteral obstruction in the neonatal rat is attenuated by IGF-1. Kidney Int 2000;57:882-90. https://doi.org/10.1046/j.1523-1755.2000.057003882.x
  70. Eddy AA. Can renal fibrosis be reversed? Pediatr Nephrol 2005;20:1369-75. https://doi.org/10.1007/s00467-005-1995-5
  71. Edgtton KL, Gow RM, Kelly DJ, Carmeliet P, Kitching AR. Plasmin is not protective in experimental renal interstitial fibrosis. Kidney Int 2004;66:68-76. https://doi.org/10.1111/j.1523-1755.2004.00707.x
  72. Cheng S, Pollock AS, Mahimkar R, Olson JL, Lovett DH. Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury. Faseb J 2006;20:1898-900. https://doi.org/10.1096/fj.06-5898fje
  73. Boor P, Sebekova K, Ostendorf T, Floege J. Treatment targets in renal fibrosis. Nephrol Dial Transplant 2007;22:3391-407. https://doi.org/10.1093/ndt/gfm393

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