Advertisement

Pediatric Nephrology

, Volume 21, Issue 11, pp 1666–1675 | Cite as

Expression profile of nephrin, podocin, and CD2AP in Chinese children with MCNS and IgA nephropathy

  • Jianhua Mao
  • Yang ZhangEmail author
  • Lizhong Du
  • Yuwen Dai
  • Chunhu Yang
  • Li Liang
Original Article

Abstract

There have been many exciting advances in our understanding of genetic causes of nephrotic syndrome since 1998 when nephrin was first found. The mRNA expressions of nephrin and CD2AP were studied by quantitative real-time polymerase chain reaction (PCR) in aspirated renal biopsy tissues from 9 subjects with minimal change nephrotic syndrome (MCNS), 6 with primary IgA nephropathy (IgAN), and 15 controls. Protein expression of nephrin, podocin, and CD2AP were analyzed by immunohistochemistry, indirect immunofluorescence, and laser confocal microscope. Compared with controls, the CD2AP mRNA level was significantly downregulated in renal samples from MCNS and IgAN patients (p=0.001 in MCNS, p=0.046 in IgAN), though no significant downregulation was found in the mRNA level of nephrin (p=0.346 in MCNS, p=0.311 in IgAN). The expression levels of protein CD2AP and nephrin were significantly reduced in MCNS and IgAN (MCNS: nephrin, p=0.034, CD2AP, p=0.005; IgAN: nephrin, p=0.021, CD2AP, p=0.025). The podocin staining did not differ significantly between controls and disease groups (p value 0.340 and 0.787, respectively). The results suggest that transcript and translation expression changes of nephrin and CD2AP may have pathogenetic roles in some patients with MCNS and IgAN in Chinese, though no correlation was found in podocin with proteinuria in this study.

Keywords

Glomerular slit diaphragm MCNS IgAN Nephrin Podocin CD2AP 

Notes

Acknowledgements

This work was supported by the Zhejiang Provincial Natural Science Foundation of China No. 302656 and the Zhejiang provincial Health Science Foundation No. 2004QN014. The authors thank Wu Yedong, Sheng Zheng, and Yu Zhongsheng for their excellent technical assistance and Drs. Xia Yonghui, Huang Yaping, and Dai Yuwen for many helpful clinical comments and advice. The authors are also grateful to Drs. Wu Dehua and Zhang Chong for providing control kidney materials to us.

References

  1. 1.
    Kestila M, Lenkkeri U, Mannikko M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K (1998) Positionally cloned gene for a novel glomerular protein—nephrin—is mutated in congenital nephrotic syndrome. Mol Cell 1:575–582CrossRefGoogle Scholar
  2. 2.
    Lenkkeri U, Mannikko M, McCready P, Lamerdin J, Gribouval O, Niaudet PM, Antignac CK, Kashtan CE, Holmberg C, Olsen A, Kestila M, Tryggvason K (1999) Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations. Am J Hum Genet 64:51–61CrossRefGoogle Scholar
  3. 3.
    Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler MC, Niaudet P, Antignac C (2000) NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 24:349–354CrossRefGoogle Scholar
  4. 4.
    Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O, Miner JH, Shaw AS (1999) Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science 286:312–315CrossRefGoogle Scholar
  5. 5.
    Kim JM, Wu H, Green G, Winkler CA, Kopp JB, Miner JH, Unanue ER, Shaw AS (2003) CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science 300:1298–1300CrossRefGoogle Scholar
  6. 6.
    Simons M, Schwarz K, Kriz W, Miettinen A, Reiser J, Mundel P, Holthofer H (2001) Involvement of lipid rafts in nephrin phosphorylation and organization of the glomerular slit diaphragm. Am J Pathol 159:1069–1077CrossRefGoogle Scholar
  7. 7.
    Chugh SS, Kaw B, Kanwar YS (2003) Molecular structure-function relationship in the slit diaphragm. Semin Nephrol 23:544–555CrossRefGoogle Scholar
  8. 8.
    Yuan H, Takeuchi E, Salant DJ (2002) Podocyte slit-diaphragm protein nephrin is linked to the actin cytoskeleton. Am J Physiol Renal Physiol 282:F585–F591CrossRefGoogle Scholar
  9. 9.
    Akhtar M, Al Mana H (2004) Molecular basis of proteinuria. Adv Anat Pathol 11:304–309CrossRefGoogle Scholar
  10. 10.
    Wartiovaara J, Ofverstedt LG, Khoshnoodi J, Zhang J, Makela E, Sandin S, Ruotsalainen V, Cheng RH, Jalanko H, Skoglund U, Tryggvason K (2004) Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography. J Clin Invest 114:1475–1483CrossRefGoogle Scholar
  11. 11.
    Liu XL, Kilpelainen P, Hellman U, Sun Y, Wartiovaara J, Morgunova E, Pikkarainen T, Yan K, Jonsson AP, Tryggvason K (2005) Characterization of the interactions of the nephrin intracellular domain. FEBS J 272:228–243CrossRefGoogle Scholar
  12. 12.
    Huber TB, Benzing T (2005) The slit diaphragm: a signaling platform to regulate podocyte function. Curr Opin Nephrol Hypertens 14:211–216CrossRefGoogle Scholar
  13. 13.
    Schachter AD (2004) The pediatric nephrotic syndrome spectrum: clinical homogeneity and molecular heterogeneity. Pediatr Transplant 8:344–348CrossRefGoogle Scholar
  14. 14.
    Koop K, Eikmans M, Baelde HJ, Kawachi H, De Heer E, Paul LC, Bruijn JA (2003) Expression of podocyte-associated molecules in acquired human kidney diseases. J Am Soc Nephrol 14:2063–2071CrossRefGoogle Scholar
  15. 15.
    Furness PN, Hall LL, Shaw JA, Pringle JH (1999) Glomerular expression of nephrin is decreased in acquired human nephrotic syndrome. Nephrol Dial Transplant 14:1234–1237CrossRefGoogle Scholar
  16. 16.
    Huh W, Kim DJ, Kim MK, Kim YG, Oh HY, Ruotsalainen V, Tryggvason K (2002) Expression of nephrin in acquired human glomerular disease. Nephrol Dial Transplant 17:478–484CrossRefGoogle Scholar
  17. 17.
    Srivastava T, Whiting JM, Garola RE, Dasouki MJ, Ruotsalainen V, Tryggvason K, Hamed R, Alon US (2001) Podocyte proteins in Galloway-Mowat syndrome. Pediatr Nephrol 16:1022–1029CrossRefGoogle Scholar
  18. 18.
    Wang SX, Rastaldi MP, Patari A, Ahola H, Heikkila E, Holthofer H (2002) Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases. Kidney Int 61:141–147CrossRefGoogle Scholar
  19. 19.
    Doublier S, Ruotsalainen V, Salvidio G, Lupia E, Biancone L, Conaldi PG, Reponen P, Tryggvason K, Camussi G (2001) Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. Am J Pathol 158:1723–1731CrossRefGoogle Scholar
  20. 20.
    Patrakka J, Ruotsalainen V, Ketola I, Holmberg C, Heikinheimo M, Tryggvason K, Jalanko H (2001) Expression of nephrin in pediatric kidney diseases. J Am Soc Nephrol 12:289–296PubMedGoogle Scholar
  21. 21.
    Guan N, Ding J, Zhang J, Yang J (2003) Expression of nephrin, podocin, alpha-actinin, and WT1 in children with nephrotic syndrome. Pediatr Nephrol 18:1122–1127CrossRefGoogle Scholar
  22. 22.
    Hingorani SR, Finn LS, Kowalewska J, McDonald RA, Eddy AA (2004) Expression of nephrin in acquired forms of nephrotic syndrome in childhood. Pediatr Nephrol 19:300–305CrossRefGoogle Scholar
  23. 23.
    Lahdenkari AT, Suvanto M, Kajantie E, Koskimies O, Kestila M, Jalanko H (2005) Clinical features and outcome of childhood minimal change nephrotic syndrome: is genetics involved? Pediatr Nephrol 20:1073–1080CrossRefGoogle Scholar
  24. 24.
    Wernerson A, Duner F, Pettersson E, Widholm SM, Berg U, Ruotsalainen V, Tryggvason K, Hultenby K, Soderberg M (2003) Altered ultrastructural distribution of nephrin in minimal change nephrotic syndrome. Nephrol Dial Transplant 18:70–76CrossRefGoogle Scholar
  25. 25.
    Salant DJ, Topham PS (2003) Role of nephrin in proteinuric renal diseases. Springer Semin Immunopathol 24:423–439CrossRefGoogle Scholar
  26. 26.
    Kim BK, Hong HK, Kim JH, Lee HS (2002) Differential expression of nephrin in acquired human proteinuric diseases. Am J Kidney Dis 40:964–973CrossRefGoogle Scholar
  27. 27.
    Gagliardini E, Benigni A, Tomasoni S, Abbate M, Kalluri R, Remuzzi G (2003) Targeted downregulation of extracellular nephrin in human IgA nephropathy. Am J Nephrol 23:277–286CrossRefGoogle Scholar
  28. 28.
    Schmid H, Henger A, Cohen CD, Frach K, Grone HJ, Schlondorff D, Kretzler M (2003) Gene expression profiles of podocyte-associated molecules as diagnostic markers in acquired proteinuric diseases. J Am Soc Nephrol 14:2958–2966CrossRefGoogle Scholar
  29. 29.
    Toyoda M, Suzuki D, Umezono T, Uehara G, Maruyama M, Honma M, Sakai T, Sakai H (2004) Expression of human nephrin mRNA in diabetic nephropathy. Nephrol Dial Transplant 19:380–385CrossRefGoogle Scholar
  30. 30.
    Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, Mathis BJ, Rodriguez-Perez JC, Allen PG, Beggs AH, Pollak MR (2000) Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 24:251–256CrossRefGoogle Scholar

Copyright information

© IPNA 2006

Authors and Affiliations

  • Jianhua Mao
    • 1
  • Yang Zhang
    • 2
    Email author
  • Lizhong Du
    • 1
  • Yuwen Dai
    • 1
  • Chunhu Yang
    • 3
  • Li Liang
    • 1
  1. 1.Department of NephrologyThe Children’s Hospital of Zhejiang University School of MedicineHangzhouPeople’s Republic of China
  2. 2.Department of EpidemiologyZhejiang University School of MedicineHangzhouPeople’s Republic of China
  3. 3.Bioelectromagnetics Laboratory, Department of Public HealthZhejiang University School of MedicineHangzhouPeople’s Republic of China

Personalised recommendations