Seminars in Nephrology
Volume 24, Issue 2 , Pages 131-140 , March 2004

Changes in glomerular perm-selectivity induced by angiotensin II imply podocyte dysfunction and slit diaphragm protein rearrangement

  • Ariela Benigni

      Affiliations

    • Mario Negri Institute for Pharmacological Research, Bergamo, Italy
    • ,
  • Elena Gagliardini

      Affiliations

    • Mario Negri Institute for Pharmacological Research, Bergamo, Italy
    • Corresponding Author InformationAddress reprint requests to Elena Gagliardini, BiolSciD, Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11, 24125 Bergamo, Italy
    • ,
  • Giuseppe Remuzzi

      Affiliations

    • Mario Negri Institute for Pharmacological Research, Bergamo, Italy
    • Unit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy

References 

  1. Bertani T, Cutillo F, Zoja C, et al.  Tubulointerstitial lesion mediate renal damage in adriamycin glomerulopathy. Kidney Int. 1986;30:488–496
  2. Eddy AA. Interstitial nephritis induced by protein-overload proteinuria. Am J Pathol. 1989;135:719–733
  3. Benigni A, Corna D, Maffi R, et al.  Renoprotective effect of contemporary blocking of angiotensin II and endothelin-1 in rats with membranous nephropathy. Kidney Int. 1998;54:353–359
  4. Remuzzi G, Bertani T. Pathophysiology of progressive nepropathies. N Engl J Med. 1998;339:1448–1456
  5. Nakajima M, Takemaka M, Kaimori JY, et al.  Gene expression profile of renal proximal tubules regulated by proteinuria. Kidney Int. 2002;61:1577–1587
  6. Wang Y, Chen J, Tay YC, et al.  Induction of monocyte chemoattrachtant protein-1 in proximal tubule cells by urinary protein. J Am Soc Nephrol. 1997;8:1537–1545
  7. Zoja C, Donadelli R, Colleoni S, et al.  Protein overload stimulates RANTES production by proximal tubular cells depending on NF-kappa B activation. Kidney Int. 1998;53:1608–1615
  8. Benigni A, Gagliardini E, Remuzzi A, et al.  Angiotensin-converting enzyme inhibition prevents glomerular-tubule disconnection and atrophy in passive Heymann nephritis, an effect not observed with calcium antagonist. Am J Pathol. 2001;159:1743–1750
  9. Erkan E, De Leon M, Devarajan P. Albumin overload induces apoptosis in LLC-PK(1) cells. Am J Physiol Renal Physiol. 2001;280:1107–1114
  10. Remuzzi G. Nephropathic nature of proteinuria. Curr Opin Nephrol Hypertens. 1999;8:655–663
  11. Taal MW, Brennner BM. Renoprotective benefits of RAS inhibition (From ACEI to angiotensin II antagonists). Kidney Int. 2000;57:1803–1817
  12. Remuzzi A, Puntorieri S, Battaglia C, et al.  Angiotensin converting enzyme inhibition ameliorates glomerular filtration of macromolecules and water and lessens glomerular injury in the rat. J Clin Invest. 1990;85:541–549
  13. Pisoni R, Ruggenenti P, Sangalli F, et al.  Effect of high dose ramipril with or without indomethacin on glomerular selectivity. Kidney Int. 2002;62:1010–1019
  14. Ruiz-Ortega M, Lorenzo O, Suzuki Y, et al.  Proinflammatory actions of angiotensins. Curr Opin Nephrol Hypertens. 2001;10:321–329
  15. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) . Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349:1857–1863
  16. Brennner BM, Cooper ME, de Zeeuw D, et al.  Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–869
  17. Tojo A, Hitoshi E. Intrarenal handling of proteins in rats using fractional micropuncture technique. Am J Physiol. 1992;263:F601–F606
  18. Remuzzi G. Abnormal protein traffic through the glomerular barrier induces proximal tubular cell dysfunction and causes renal injury. Curr Opin Nephrol Hypertens. 1995;4:339–342
  19. Remuzzi G, Bertani T. Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules?. Kidney Int. 1990;38:384–394
  20. Yoshioka T, Rennke HG, Salant DJ, et al.  Role of abnormally high transmural pressure in the permselectivity defect of glomerular capillary wall (A study in early passive Heymann nephritis). Circ Res. 1987;61:531–538
  21. Tryggvason K, Wartiovaara J. Molecular basis of glomerular permselectivity. Curr Opin Nephrol Hypertens. 2001;10:543–549
  22. Somlo S, Mundel P. Getting a foothold in nephrotic syndrome. Nat Genet. 2000;24:333–335
  23. Rodewald R, Karnovsky MJ. Porous substructure of the glomerular slit diaphragm in the rat and mouse. J Cell Biol. 1974;60:423–433
  24. Schnabel E, Anderson JM, Farquhar MG. The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium. J Cell Biol. 1990;111:1255–1263
  25. Inoue T, Yaoita E, Kurihara H, et al.  FAT is a component of glomerular slit diaphragms. Kidney Int. 2001;59:1003–1012
  26. Putaala H, Soininen R, Kilpelainen P, et al.  The murine nephrin gene is specifically expressed in kidney, brain and pancreas (Inactivation of the gene leads to massive proteinuria and neonatal death). Hum Mol Genet. 2001;10:1–8
  27. Liu L, Aya K, Tanaka H, et al.  Nephrin is an important component of the barrier system in the testis. Acta Med Okayama. 2001;55:161–165
  28. Tryggvason K. Unraveling the mechanisms of glomerular ultrafiltration (Nephrin, a key component of the slit diaphragm). J Am Soc Nephrol. 1999;10:2440–2445
  29. Lahdenpera J, Kilpelainen P, Li Liu X, et al.  Clustering-induced tyrosine phosphorylation of nephrin by Src family kinases. Kidney Int. 2003;64:404–413
  30. Mathieson PW. Nephrin sends us signals. Kidney Int. 2003;64:756–757
  31. Patrakka J, Kestila M, Wartiovaara J, et al.  Congenital nephrotic syndrome (NPHS1) (Features resulting from different mutations in Finnish patients). Kidney Int. 2000;58:972–980
  32. Lenkkeri U, Mannikko M, McCready P, et al.  Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations. Am J Hum Genet. 1999;64:51–61
  33. Hamano Y, Grunkemeyer JA, Sudhakar A, et al.  Determinants of vascular permeability in the kidney glomerulus. J Biol Chem. 2002;277:31154–31162
  34. Boute N, Gribouval O, Roselli S, et al.  NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet. 2000;24:349–354
  35. Schwarz K, Simons M, Reiser J, et al.  Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J Clin Invest. 2001;108:1621–1629
  36. Sellin L, Huber TB, Gerke P, et al.  NEPH1 defines a novel family of podocin interacting proteins. FASEB J. 2003;17:115–117
  37. Simons M, Schwarz K, Kriz W, et al.  Involvement of lipid rafts in nephrin phosphorylation and organization of the glomerular slit diaphragm. Am J Pathol. 2001;159:1069–1077
  38. Dustin ML, Olszowy MW, Holdorf AD, et al.  A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell. 1998;94:667–677
  39. Shih NY, Li J, Karpitskii V, et al.  Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science. 2001;286:312–315
  40. Palmen T, Lehtonen S, Ora A, et al.  Interaction of endogenous nephrin and CD2-associated protein in mouse epithelial M-1 cell line. J Am Soc Nephrol. 2002;13:1766–1772
  41. Yuan H, Takeuchi E, Salant DJ. Podocyte slit-diaphragm protein nephrin is linked to the actin cytoskeleton. Am J Physiol Renal Physiol. 2002;282:F585–F591
  42. Kim JM, Wu H, Green G, et al.  CD-2 associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science. 2003;300:1298–1300
  43. Barletta GM, Kovari IA, Verma RK, et al.  Nephrin and Neph1 co-localized at the podocyte foot process intercellular junction and form cis hetero-oligomers. J Biol Chem. 2003;278:19266–19271
  44. Huber TB, Schmidts M, Gerke P, et al.  The carboxyl terminus of Neph family members binds to the PDZ domain protein zonula occludens-1. J Biol Chem. 2003;278:13417–13421
  45. Huber TB, Kottgen M, Shilling B, et al.  Interaction with podocin facilitates nephrin signaling. J Biol Chem. 2001;276:41543–41546
  46. Saleem MA, Ni L, Wntherden I, et al.  Co-localization of nephrin podocin and the actin cytoskeleton (Evidence for a role in podocyte foot process formation). Am J Pathol. 2002;161:1459–1466
  47. Lapinski R, Perico N, Remuzzi A, et al.  Angiotensin II modulates glomerular capillary permselectivity in rat isolated perfused kidney. J Am Soc Nephrol. 1996;7:653–660
  48. Anderson S, Meyer TW, Rennke HG, Brenner BM. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest. 1985;76:612–619
  49. Zatz R, Dunn BR, Meyer TW, et al.  Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest. 1986;77:1925–1930
  50. Hommel E, Parving HH, Mathiesen E, et al.  Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy. BMJ. 1986;293:467–470
  51. Lewis EJ, Hunsicker LG, Bain RP, et al.  The effect of angiotensin converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Eng J Med. 1993;329:1456–1462
  52. Remuzzi A, Puntorieri S, Alfano M, et al.  Pathophysiologic implications of proteinuria in a rat model of progressive glomerular injury. Lab Invest. 1992;67:572–579
  53. Remuzzi A, Malanchini B, Battaglia C, et al.  Comparison of the effects of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade on the evolution of spontaneous glomerular injury in male MwF/Ztm rats. Exp Nephrol. 1996;4:19–25
  54. Parving HH, Hommel E, Smidt UM. Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy. BMJ. 1988;297:1086–1091
  55. Heeg JE, De Jong PE, Van Der Hem GK, de Zeeuw D. Reduction of proteinuria by angiotensin converting enzyme inhibition. Kidney Int. 1987;32:78–83
  56. Remuzzi A, Perticucci E, Ruggenenti P, et al.  Angiotensin converting enzyme inhibition improves glomerular size-selectivity in IgA nephropathy. Kidney Int. 1991;39:1267–1273
  57. Ene-Iordache B, Imberti O, Foglieni C, et al.  Effects of angiotensin-converting enzyme inhibition on glomerular capillary wall ultrastructure in MWF/Ztm rats. J Am Soc Nephrol. 1994;5:1378–1384
  58. Macconi D, Ghilardi M, Bonassi ME, et al.  Effect of angiotensin-converting enzyme inhibition on glomerular basement membrane permeability and distribution of zonula occludens-1 in MWF rats. J Am Soc Nephrol. 2000;11:477–489
  59. Orikasa M, Matsui K, Oite T, Shimizu F. Massive proteinuria induced in rats by a single intravenous injection of a monoclonal antibody. J Immunol. 1988;141:807–814
  60. Topham PS, Kawachi H, Haydar SA, et al.  Nephritogenic mAb 5-1-6 is directed at the extracellular domain of rat nephrin. J Clin Invest. 1999;104:1559–1566
  61. Luimula P, Sandstrom N, Novikov D, Holthofer H. Podocyte-associated molecules in puromycin aminonucleoside nephrosis of the rat. Lab Invest. 2002;82:713–718
  62. Okasora T, Nagase M, Kawachi H, et al.  Altered localization of antigen recognized by proteinuria-inducing monoclonal antibody in experimental nephrosis. Virchows Arch. 1991;60:41–46
  63. Luimula P, Aaltonen P, Ahola H, et al.  Alternatively spliced nephrin in experimental glomerular disease of the rat. Pediatr Res. 2000;48:759–762
  64. Luimula P, Ahola H, Wang SX, et al.  Nephrin in experimental glomerular disease. Kidney Int. 2000;58:1461–1468
  65. Yuan H, Takeuchi E, Taylor GA, et al.  Nephrin dissociates from actin, and its expression is reduced in early experimental membranous nephropathy. J Am Soc Nephrol. 2002;13:946–956
  66. Cao Z, Bonnet F, Candido R, et al.  Angiotensin type 2 receptor antagonsim confers renal protection in a rat model of progressive renal injury. J Am Soc Nephrol. 2002;13:1773–1787
  67. Endlich N, Kress KR, Reiser J, et al.  Podocytes respond to mechanical stress in vitro. J Am Soc Nephrol. 2001;12:413–422
  68. Macconi D, Ghilardi M, Bonassi ME, et al.  Effect of angiotensin-converting enzyme inhibition on glomerular basement membrane permeability and distribution of zonula occludens-1 in MWF rats. J Am Soc Nephrol. 2000;11:477–489
  69. Reiser J, Kriz W, Kretzler M, Mundel P. The glomerular slit diaphragm is a modified adherens junction. J Am Soc Nephrol. 2000;11:1–8s
  70. Aaltonen P, Luimula P, Astrom E, et al.  Changes in the expression of nephrin gene and protein in experimental diabetic nephropathy. Lab Invest. 2001;8:1185–1190
  71. Kelly DJ, Aaaltonen P, Cox AJ, et al.  Expression of the slit-diaphragm protein, nephrin, in experimental diabetic nephropathy (Differing effect of anti-proteinuric therapies). Nephrol Dial Transplant. 2002;17:1327–1332
  72. Bonnet F, Cooper ME, Kawachi H, et al.  Irbesartan normalises the deficiency in glomerular nephrin expression in a model of diabetes and hypertension. Diabetologia. 2001;44:874–877
  73. Davis BJ, Cao Z, De Gasparo M, et al.  Disparate effects of angiotensin II antagonists and calcium channel blockers on albuninuria in experimental diabetes and hypertension (Potential role of nephrin). J Hypertens. 2003;21:209–216
  74. Davis BJ, Johnston CI, Burrel LM, et al.  Renoprotective effects of vasopeptidase inhibition in an experimental model of diabetic nephropathy. Diabetologia. 2003;46:961–971
  75. Furness PN, Hall LL, Shaw JA, Pringle JH. Glomerular expression of nephrin is decreased in acquired human nephrotic syndrome. Nephrol Dial Transplant. 1999;14:1234–1237
  76. Patrakka J, Ruotsalainen V, Ketola I, et al.  Expression of nephrin in pediatric kidney diseases. J Am Soc Nephrol. 2001;12:289–296
  77. Wang S-X, Rastaldi MP, Patari A, et al.  Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases. Kidney Int. 2002;61:141–147
  78. Doublier S, Ruotsalainen V, Salvidio G, et al.  Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. Am J Pathol. 2001;158:1723–1731
  79. Wernerson A, Duner F, Pettersson E, et al.  Altered ultrastructural distribution of nephrin in minimal change nephrotic syndrome. Nephrol Dial Transplant. 2003;18:70–76
  80. Gagliardini E, Benigni A, Tomasoni S, et al.  Targeted downregulation of extracellular nephrin in human IgA nephropathy. Am J Nephrol. 2003;23:277–286
  81. Langham RG, Kelly DJ, Cox AJ, et al.  Proteinuria and the expression of the podocyte slit diaphragm protein, nephrin, in diabetic nephropathy (Effects of angiotensin converting enzyme inhbition). Diabetologia. 2002;45:1572–1576
  82. Doublier S, Salvidio G, Lupia E, et al.  Nephrin expression is reduced in human diabetic nephropathy. Evidence for a distinct role for glycated albumin and angiotensin II. Diabetes. 2003;52:1023–1030
  83. Benigni A, Gagliardini E, Tomasoni S, et al: Selective impairment of gene expression and assembly of nephrin in human diabetic nephropathy. Kidney Int (in press)
  84. Pettersson-Fernholm K, Forsblom C, Perola M, et al.  Polymorphisms in the nephrin gene and diabetic nephropathy in type 1 diabetic patients. Kidney Int. 2003;63:1205–1210
  85. Iyengar SK, Fox KA, Schachere M, et al.  Linkage analysis of candidate loci for end-stage renal disease due to diabetic nephropathy. J Am Soc Nephrol. 2003;14:S195–S201

PII: S0270-9295(03)00195-5

doi: 10.1016/j.semnephrol.2003.11.005

Seminars in Nephrology
Volume 24, Issue 2 , Pages 131-140 , March 2004

Article Tools

* Image Usage & Resolution