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International Journal of Nephrology
Volume 2012, Article ID 749010, 9 pages
http://dx.doi.org/10.1155/2012/749010
Review Article

The Glomerular Filtration Barrier: Components and Crosstalk

1Division of Nephrology, Mount Sinai School of Medicine, New York, NY 10029, USA
2Division of Nephrology, James J. Peters VA Medical Center, Bronx, NY 10468, USA

Received 22 March 2012; Revised 2 June 2012; Accepted 5 June 2012

Academic Editor: Omran Bakoush

Copyright © 2012 Madhav C. Menon et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. C. Peterson, S. Adler, J. M. Burkart et al., “Blood pressure control, proteinuria, and the progression of renal disease: the modification of diet in renal disease study,” Annals of Internal Medicine, vol. 123, no. 10, pp. 754–762, 1995. View at Google Scholar · View at Scopus
  2. C. Chronic Kidney Disease Prognosis, K. Matsushita, M. van der Velde et al., “Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis,” The Lancet, vol. 375, no. 9731, pp. 2073–2081, 2010. View at Google Scholar
  3. M. F. Carroll and J. L. Temte, “Proteinuria in adults: a diagnostic approach,” American Family Physician, vol. 62, no. 6, pp. 1333–1340, 2000. View at Google Scholar · View at Scopus
  4. J. Barratt and P. Topham, “Urine proteomics: the present and future of measuring urinary protein components in disease,” Canadian Medical Association Journal, vol. 177, no. 4, pp. 361–368, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. L. M. Russo, R. M. Sandoval, M. McKee et al., “The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: retrieval is disrupted in nephrotic states,” Kidney International, vol. 71, no. 6, pp. 504–513, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. G. A. Tanner, “Glomerular sieving coefficient of serum albumin in the rat: a two-photon microscopy study,” American Journal of Physiology, vol. 296, no. 6, pp. F1258–F1265, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. J. Peti-Peterdi, “Independent two-photon measurements of albumin GSC give low values,” American Journal of Physiology, vol. 296, no. 6, pp. F1255–F1257, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Tojo and H. Endou, “Intrarenal handling of proteins in rats using fractional micropuncture technique,” American Journal of Physiology, vol. 263, no. 4, pp. F601–F606, 1992. View at Google Scholar · View at Scopus
  9. H. Pavenstädt, W. Kriz, and M. Kretzler, “Cell biology of the glomerular podocyte,” Physiological Reviews, vol. 83, no. 1, pp. 253–307, 2003. View at Google Scholar · View at Scopus
  10. V. D. D'Agati, F. J. Kaskel, and R. J. Falk, “Focal segmental glomerulosclerosis,” The New England Journal of Medicine, vol. 365, no. 25, pp. 2398–2411, 2011. View at Publisher · View at Google Scholar
  11. B. G. Hudson, K. Tryggvason, M. Sundaramoorthy, and E. G. Neilson, “Alport's syndrome, Goodpasture's syndrome, and type IV collagen,” The New England Journal of Medicine, vol. 348, no. 25, pp. 2543–2556, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Noris and G. Remuzzi, “Atypical hemolytic-uremic syndrome,” The New England Journal of Medicine, vol. 361, no. 17, pp. 1676–1687, 2009. View at Google Scholar · View at Scopus
  13. J. L. Ambrus Jr. and N. R. Sridhar, “Immunologic aspects of renal disease,” Journal of the American Medical Association, vol. 278, no. 22, pp. 1938–1945, 1997. View at Google Scholar · View at Scopus
  14. D. Kerjaschki, D. J. Sharkey, and M. G. Farquhar, “Identification and characterization of podocalyxin—the major sialoprotein of the renal glomerular epithelial cell,” Journal of Cell Biology, vol. 98, no. 4, pp. 1591–1596, 1984. View at Google Scholar · View at Scopus
  15. E. Schnabel, J. M. Anderson, and M. G. Farquhar, “The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium,” Journal of Cell Biology, vol. 111, no. 3, pp. 1255–1263, 1990. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Reiser, W. Kriz, M. Kretzler, and P. Mundel, “The glomerular slit diaphragm is a modified adherens junction,” Journal of the American Society of Nephrology, vol. 11, no. 1, pp. 1–8, 2000. View at Google Scholar · View at Scopus
  17. V. Ruotsalainen, P. Ljungberg, J. Wartiovaara et al., “Nephrin is specifically located at the slit diaphragm of glomerular podocytes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 14, pp. 7962–7967, 1999. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Wartiovaara, L. G. Öfverstedt, J. Khoshnoodi et al., “Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography,” Journal of Clinical Investigation, vol. 114, no. 12, article 1820, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. G. Liu, B. Kaw, J. Kurfis, S. Rahmanuddin, Y. S. Kanwar, and S. S. Chugh, “Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability,” Journal of Clinical Investigation, vol. 112, no. 2, pp. 209–221, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. J. M. Kaplan, S. H. Kim, K. N. North et al., “Mutations in ACTN4, encoding α-actinin-4, cause familial focal segmental glomerulosclerosis,” Nature Genetics, vol. 24, no. 3, pp. 251–256, 2000. View at Publisher · View at Google Scholar · View at Scopus
  21. E. J. Brown, J. S. Schlöndorff, D. J. Becker et al., “Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis,” Nature Genetics, vol. 42, no. 1, pp. 72–76, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. H. Ma, A. Togawa, K. Soda et al., “Inhibition of podocyte FAK protects against proteinuria and foot process effacement,” Journal of the American Society of Nephrology, vol. 21, no. 7, pp. 1145–1156, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. A. J. W. Branten, J. Van den Born, J. L. J. Jansen, K. J. M. Assmann, J. F. M. Wetzels, and H. B. P. M. Dijkman, “Familial nephropathy differing from minimal change nephropathy and focal glomerulosclerosis,” Kidney International, vol. 59, no. 2, pp. 693–701, 2001. View at Publisher · View at Google Scholar · View at Scopus
  24. D. Macconi, M. Ghilardi, M. E. Bonassi et al., “Effect of angiotensin-converting enzyme inhibition on glomerular basement membrane permeability and distribution of zonula occludens-1 in MWF rats,” Journal of the American Society of Nephrology, vol. 11, no. 3, pp. 477–489, 2000. View at Google Scholar · View at Scopus
  25. S. A. Karumanchi, S. E. Maynard, I. E. Stillman, F. H. Epstein, and V. P. Sukhatme, “Preeclampsia: a renal perspective,” Kidney International, vol. 67, no. 6, pp. 2101–2113, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. B. L. Wharram, M. Goyal, P. J. Gillespie et al., “Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate,” Journal of Clinical Investigation, vol. 106, no. 10, pp. 1281–1290, 2000. View at Google Scholar · View at Scopus
  27. J. G. van den Berg, M. A. van den Bergh Weerman, K. J. M. Assmann, J. J. Weening, and S. Florquin, “Podocyte foot process effacement is not correlated with the level of proteinuria in human glomerulopathies,” Kidney International, vol. 66, no. 5, pp. 1901–1906, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. M. W. Seiler, M. A. Venkatachalam, and R. S. Cotran, “Glomerular epithelium: structural alterations induced by polycations,” Science, vol. 189, no. 4200, pp. 390–393, 1975. View at Google Scholar · View at Scopus
  29. P. Garg, R. Verma, L. Cook et al., “Actin-depolymerizing factor cofilin-1 is necessary in maintaining mature podocyte architecture,” Journal of Biological Chemistry, vol. 285, no. 29, pp. 22676–22688, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. J. H. Kim, H. Wu, G. Green et al., “CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility,” Science, vol. 300, no. 5623, pp. 1298–1300, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. C. Wei and J. Reiser, “Minimal change disease as a modifiable podocyte paracrine disorder,” Nephrology Dialysis Transplantation, vol. 26, no. 6, pp. 1776–1777, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. P. Garg and T. Rabelink, “Glomerular proteinuria: a complex interplay between unique players,” Advances in Chronic Kidney Disease, vol. 18, no. 4, pp. 233–242, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. J. Reiser, J. Oh, I. Shirato et al., “Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and α3 integrin,” Journal of Biological Chemistry, vol. 279, no. 33, pp. 34827–34832, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Adler and X. Chen, “Anti-Fx1A antibody recognizes a β1-integrin on glomerular epithelial cells and inhibits adhesion and growth,” American Journal of Physiology, vol. 262, no. 5, pp. F770–F776, 1992. View at Google Scholar · View at Scopus
  35. C. El-Aouni, N. Herbach, S. M. Blattner et al., “Podocyte-specific deletion of integrin-linked kinase results in severe glomerular basement membrane alterations and progressive glomerulosclerosis,” Journal of the American Society of Nephrology, vol. 17, no. 5, pp. 1334–1344, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. Y. S. Kang, Y. Li, C. Dai, L. P. Kiss, C. Wu, and Y. Liu, “Inhibition of integrin-linked kinase blocks podocyte epithelial-mesenchymal transition and ameliorates proteinuria,” Kidney International, vol. 78, no. 4, pp. 363–373, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. F. Blasi and P. Carmeliet, “uPAR: a versatile signalling orchestrator,” Nature Reviews Molecular Cell Biology, vol. 3, no. 12, pp. 932–943, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. H. W. Smith and C. J. Marshall, “Regulation of cell signalling by uPAR,” Nature Reviews Molecular Cell Biology, vol. 11, no. 1, pp. 23–36, 2010. View at Publisher · View at Google Scholar
  39. C. Wei, C. C. Moller, M. M. Altintas, " et al., “Modification of kidney barrier function by the urokinase receptor,” Nature Medicine, vol. 14, no. 1, pp. 55–63, 2008. View at Publisher · View at Google Scholar
  40. C. Wei, S. El Hindi, J. Li et al., “Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis,” Nature Medicine, vol. 17, no. 8, pp. 952–960, 2011. View at Publisher · View at Google Scholar
  41. G. E. Striker and E. A. Smuckler, “An ultrastructural study of glomerular basement membrane synthesis,” American Journal of Pathology, vol. 58, no. 3, pp. 531–565, 1970. View at Google Scholar · View at Scopus
  42. D. R. Abrahamson, “Structure and development of the glomerular capillary wall and basement membrane,” American Journal of Physiology, vol. 253, no. 5, pp. F783–F794, 1987. View at Google Scholar · View at Scopus
  43. J. R. Sanes, E. Engvall, R. Butkowski, and D. D. Hunter, “Molecular heterogeneity of basal laminae: isoforms of laminin and collagen IV at the neuromuscular junction and elsewhere,” Journal of Cell Biology, vol. 111, no. 4, pp. 1685–1699, 1990. View at Google Scholar · View at Scopus
  44. R. Kalluri and D. Cosgrove, “Assembly of Type IV collagen. Insights from α3(IV) collagen-deficient mice,” Journal of Biological Chemistry, vol. 275, no. 17, pp. 12719–12724, 2000. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Zenker, T. Aigner, O. Wendler et al., “Human laminin β2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities,” Human Molecular Genetics, vol. 13, no. 21, pp. 2625–2632, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. P. G. Noakes, J. H. Miner, M. Gautam, J. M. Cunningham, J. R. Sanes, and J. P. Merlie, “The renal glomerulus of mice lacking S-laminin/laminin β2: nephrosis despite molecular compensation by laminin β1,” Nature Genetics, vol. 10, no. 4, pp. 400–406, 1995. View at Google Scholar · View at Scopus
  47. W. H. Reeves, Y. S. Kanwar, and M. Gist Farquhar, “Assembly of the glomerular filtration surface. Differentiation of anionic sites in glomerular capillaries of newborn rat kidney,” Journal of Cell Biology, vol. 85, no. 3, pp. 735–753, 1980. View at Google Scholar · View at Scopus
  48. Y. S. Kanwar and M. G. Farquhar, “Anionic sites in the glomerular basement membrane. In vivo and vitro localization to the laminae rarae by cationic probes,” Journal of Cell Biology, vol. 81, no. 1, pp. 137–153, 1979. View at Google Scholar · View at Scopus
  49. Y. S. Kanwar, A. Linker, and M. G. Farquhar, “Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion,” Journal of Cell Biology, vol. 86, no. 2, pp. 688–693, 1980. View at Google Scholar · View at Scopus
  50. G. R. Bolton, W. M. Deen, and B. S. Daniels, “Assessment of the charge selectivity of glomerular basement membrane using Ficoll sulfate,” American Journal of Physiology, vol. 274, no. 5, pp. F889–F896, 1998. View at Google Scholar · View at Scopus
  51. B. S. Daniels, “Increased albumin permeability in vitro following alterations of glomerular charge is mediated by the cells of the filtration barrier,” Journal of Laboratory and Clinical Medicine, vol. 124, no. 2, pp. 224–230, 1994. View at Google Scholar · View at Scopus
  52. A. Guasch, W. M. Deen, and B. D. Myers, “Charge selectivity of the glomerular filtration barrier in healthy and nephrotic humans,” Journal of Clinical Investigation, vol. 92, no. 5, pp. 2274–2282, 1993. View at Google Scholar · View at Scopus
  53. S. Chen, D. J. Wassenhove-McCarthy, Y. Yamaguchi et al., “Loss of heparan sulfate glycosaminoglycan assembly in podocytes does not lead to proteinuria,” Kidney International, vol. 74, no. 3, pp. 289–299, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. L. C. Clement, C. Avila-Casado, C. MacÉ et al., “Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome,” Nature Medicine, vol. 17, no. 1, pp. 117–122, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. B. J. Ballermann, “Contribution of the endothelium to the glomerular permselectivity barrier in health and disease,” Nephron, vol. 106, no. 2, pp. p19–p25, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Jeansson and B. Haraldsson, “Glomerular size and charge selectivity in the mouse after exposure to glucosaminoglycan-degrading enzymes,” Journal of the American Society of Nephrology, vol. 14, no. 7, pp. 1756–1765, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. C. Hjalmarsson, B. R. Johansson, and B. Haraldsson, “Electron microscopic evaluation of the endothelial surface layer of glomerular capillaries,” Microvascular Research, vol. 67, no. 1, pp. 9–17, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. V. Fridén, E. Oveland, O. Tenstad et al., “The glomerular endothelial cell coat is essential for glomerular filtration,” Kidney International, vol. 79, no. 12, pp. 1322–1330, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. H. Kerr and A. Richards, “Complement-mediated injury and protection of endothelium: lessons from atypical haemolytic uraemic syndrome,” Immunobiology, vol. 217, no. 2, pp. 195–203, 2012. View at Publisher · View at Google Scholar
  60. N. Besbas, D. Karpman, D. Landau et al., “A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders,” Kidney International, vol. 70, no. 3, pp. 423–431, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. T. Manuelian, J. Hellwage, S. Meri et al., “Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome,” Journal of Clinical Investigation, vol. 111, no. 8, pp. 1181–1190, 2003. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Heinen, M. Józsi, A. Hartmann et al., “Hemolytic uremic syndrome: a factor H mutation (E1172Stop) causes defective complement control at the surface of endothelial cells,” Journal of the American Society of Nephrology, vol. 18, no. 2, pp. 506–514, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Richards, E. J. Kemp, M. K. Liszewski et al., “Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 22, pp. 12966–12971, 2003. View at Publisher · View at Google Scholar · View at Scopus
  64. R. R. Foster, R. Hole, K. Anderson et al., “Functional evidence that vascular endothelial growth factor may act as an autocrine factor on human podocytes,” American Journal of Physiology, vol. 284, no. 6, pp. F1263–F1273, 2003. View at Google Scholar · View at Scopus
  65. V. Eremina and S. E. Quaggin, “The role of VEGF-A in glomerular development and function,” Current Opinion in Nephrology and Hypertension, vol. 13, no. 1, pp. 9–15, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. K. Sison, V. Eremina, H. Baelde et al., “Glomerular structure and function require paracrine, not autocrine, VEGF-VEGFR-2 signaling,” Journal of the American Society of Nephrology, vol. 21, no. 10, pp. 1691–1701, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. V. Eremina, M. Sood, J. Haigh et al., “Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases,” Journal of Clinical Investigation, vol. 111, no. 5, pp. 707–716, 2003. View at Publisher · View at Google Scholar · View at Scopus
  68. S. E. Maynard, J. Y. Min, J. Merchan et al., “Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction hypertension, and proteinuria in preeclampsia,” Journal of Clinical Investigation, vol. 111, no. 5, pp. 649–658, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. V. Eremina, J. A. Jefferson, J. Kowalewska et al., “VEGF inhibition and renal thrombotic microangiopathy,” The New England Journal of Medicine, vol. 358, no. 11, pp. 1129–1136, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. L. G. Presta, H. Chen, S. J. O'Connor et al., “Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders,” Cancer Research, vol. 57, no. 20, pp. 4593–4599, 1997. View at Google Scholar · View at Scopus
  71. X. Zhu, S. Wu, W. L. Dahut, and C. R. Parikh, “Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis,” American Journal of Kidney Diseases, vol. 49, no. 2, pp. 186–193, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. H. Izzedine, I. Brocheriou, G. Deray, and O. Rixe, “Thrombotic microangiopathy and anti-VEGF agents,” Nephrology Dialysis Transplantation, vol. 22, no. 5, pp. 1481–1482, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Takabatake, T. Sugiyama, H. Kohara et al., “The CXCL12 (SDF-1)/CXCR4 axis is essential for the development of renal vasculature,” Journal of the American Society of Nephrology, vol. 20, no. 8, pp. 1714–1723, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. T. N. Petruzziello-Pellegrini, D. A. Yuen, A. V. Page et al., “The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice,” Journal of Clinical Investigation, vol. 122, no. 2, pp. 759–776, 2012. View at Publisher · View at Google Scholar
  75. D. Schlöndorff, “Roles of the mesangium in glomerular function,” Kidney International, vol. 49, no. 6, pp. 1583–1585, 1996. View at Google Scholar · View at Scopus
  76. P. Leveen, M. Pekny, S. Gebre-Medhin, B. Swolin, E. Larsson, and C. Betsholtz, “Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities,” Genes and Development, vol. 8, no. 16, pp. 1875–1887, 1994. View at Google Scholar · View at Scopus
  77. P. Soriano, “Abnormal kidney development and hematological disorders in PDGF β- receptor mutant mice,” Genes and Development, vol. 8, no. 16, pp. 1888–1896, 1994. View at Google Scholar · View at Scopus
  78. T. Yamamoto, C. A. Mundy, C. B. Wilson, and R. C. Blantz, “Effect of mesangial cell lysis and proliferation on glomerular hemodynamics in the rat,” Kidney International, vol. 40, no. 4, pp. 705–713, 1991. View at Google Scholar · View at Scopus
  79. L. Buschhausen, S. Seibold, O. Gross, T. Matthaeus, M. Weber, and E. Schulze-Lohoff, “Regulation of mesangial cell function by vasodilatory signaling molecules,” Cardiovascular Research, vol. 51, no. 3, pp. 463–469, 2001. View at Publisher · View at Google Scholar · View at Scopus
  80. F. N. Ziyadeh, K. Sharma, M. Ericksen, and G. Wolf, “Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-β,” Journal of Clinical Investigation, vol. 93, no. 2, pp. 536–542, 1994. View at Google Scholar · View at Scopus
  81. F. Zheng, F. Cornacchia, I. Schulman et al., “Development of albuminuria and glomerular lesions in normoglycemic B6 recipients of db/db mice bone marrow: the role of mesangial cell progenitors,” Diabetes, vol. 53, no. 9, pp. 2420–2427, 2004. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Tomana, J. Novak, B. A. Julian, K. Matousovic, K. Konecny, and J. Mestecky, “Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies,” Journal of Clinical Investigation, vol. 104, no. 1, pp. 73–81, 1999. View at Google Scholar · View at Scopus
  83. K. N. Lai, S. C. W. Tang, J. Y. Guh et al., “Polymeric IgA1 from patients with IgA nephropathy upregulates transforming growth factor-β synthesis and signal transduction in human mesangial cells via the renin-angiotensin system,” Journal of the American Society of Nephrology, vol. 14, no. 12, pp. 3127–3137, 2003. View at Publisher · View at Google Scholar · View at Scopus
  84. K. N. Lai, J. C. K. Leung, L. Y. Y. Chan et al., “Activation of podocytes by mesangial-derived TNF-α: glomerulo-podocytic communication in IgA nephropathy,” American Journal of Physiology, vol. 294, no. 4, pp. F945–F955, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. D. Del Prete, G. Gambaro, A. Lupo et al., “Precocious activation of genes of the renin-angiotensin system and the fibrogenic cascade in IgA glomerulonephritis,” Kidney International, vol. 64, no. 1, pp. 149–159, 2003. View at Publisher · View at Google Scholar · View at Scopus