ABSTRACT Background Podocyte injury probably plays important roles in the pathogenesis of IgA nephropathy (IgAN). We studied intra-renal and urinary messenger RNA (mRNA) expression of podocyte-associated molecules in patients with IgAN. Methods We studied 43 consecutive patients with biopsy-proven IgAN. Intra-renal and urinary expression of mRNAs was determined and compared to that of 20 patients with nephrectomy for kidney cancer and 12 normal subjects. Results Intra-renal mRNA expression levels of nephrin, podocin and synaptopodin were significantly lower in patients with IgAN than that of controls. In contrast, their urinary mRNA expression levels were similar. Intra-renal gene expression of nephrin inversely correlated with proteinuria (r = –0.620, P < 0.001), GFR (r = 0.538, P < 0.001), and the degree of tubulointerstitial scarring (r = –0.423, P = 0.013). After followed for an average of 33.4 ? 12.6 months, intra-renal nephrin expression significantly correlated with the rate of GFR decline (r = 0.324, P = 0.041). Conclusions Intra-renal mRNA expression of podocyte associated molecules was down-regulated in patients with IgAN, and the degree of down-
regulation of nephrin correlated with disease severity and the rate of progression. Our result supports the hypothesis that podocyte injury is an important component in the pathophysiology of IgAN.
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nullWang, G. , Kwan, B. , Lai, F. , Choi, P. , Chow, K. , Li, P. and Szeto, C. (2010) Intra-renal and urinary RNA expression of podcyte-associated molecules in patients with IgA nephropathy. Advances in Bioscience and Biotechnology, 1, 232-237. doi: 10.4236/abb.2010.13032.
 Donadio, J.V. and Grande, J.P. (2002) IgA nephropathy. New England Journal of Medicine, 347(10), 738-748.
Berthoux, F.C., Mohey, H. and Afiani, A. (2008) Natural history of primary IgA nephropathy. Seminars in Nephrology, 28(1), 4-9.
Tan, C.H., Loh, P.T., Yang, W.S., Chan, C.M. (2008) Mycophenolate mofetil in the treatment of IgA nephropathy: A systematic review. Singapore Medical Journal, 49(10), 780-785.
Lemley, K.V., Lafayette, R.A., Safai, M., Derby, G., Blouch, K., Squarer, A. and Myers, B.D. (2002) Podocytopenia and disease severity in IgA nephropathy. Kidney International, 61(4), 1475-1485.
Hishiki, T., Shirato, I., Takahashi, Y., Funabiki, K., Horikoshi, S., Tomino, Y. (2001) Podocyte injury predicts prognosis in patients with IgA nephropathy using a small amount of renal biopsy tissue. Kidney and Blood Pressure Research, 24(2), 99-104.
Qiu, L.Q., Sinniah, R., IHH, S. (2004) Downregulation of Bcl-2 by podocytes is associated with progressive glomerular injury and clinical indices of poor renal prognosis in human IgA nephropathy. Journal of the American Society of Nephrology, 15(1), 79-90.
Lai, K.N., Leung, J.C., Chan, L.Y., Saleem, M.A., Mathieson, P.W., Tam, K.Y., Xiao, J., Lai, F.M. and Tang, S.C. (2009) Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy. Nephrology Dialysis Transplantation, 24(1), 62-72.
Levey, A.S., Bosch, J.P., Lewis, J.B., Greene, T., Rogers, N. and Roth, D. (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Annals of Internal Medicine, 130(6), 461-470.
Mitch, W. (1986) Measuring the rate of progression of renal insufficiency. In: Mitch, W., Stein, J. and Brenner, B., Eds., The Progressive Nature of Renal Disease, Churchill Livingstone Inc, New York, 203-220.
Bhandari, S., Watson, N., Long, E., Sharpe, S., Zhong, W., Xu, S.Z. and Atkin, S.L. (2008) Expression of somatostatin and somatostatin receptor subtypes 1-5 in human normal and diseased kidney. Journal of Histochemistry & Cytochemistry, 56(8), 733-743.
Wang, C., Peng, H., Tang, H., Liu, X., Chen, Z., Lou, T. and Yu, X. (2007) Serum IgA1 from IgA nephropathy patients induces apoptosis in podocytes through direct and indirect pathways. Clinical and Investigative Medicine, 30(6), E240-249.
Hara, M., Yanagihara, T. and Kihara, I. (2007) Cumulative excretion of urinary podocytes reflects disease progression in IgA nephropathy and Schonlein-Henoch purpura nephritis. Clinical Journal of the American Society of Nephrology, 2(2), 231-238.
Ng, W.L., Chan, K.W., Yeung, C.K. and Kwan, S. (1984) Peripheral glomerular capillary wall lesions in IgA nephropathy and their implications. Pathology, 16(3), 324- 330.
Gagliardini, E., Benigni, A., Tomasoni, S., Abbate, M., Kalluri, R. and Remuzzi, G. (2003) Targeted downregulation of extracellular nephrin in human IgA nephropathy. American Journal of Nephrology, 23(4), 277-286.
Doublier, S., Ruotsalainen, V., Salvidio, G., Lupia, E., Biancone, L., Conaldi, P.G., Reponen, P., Tryggvason, K. and Camussi, G. (2001) Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. American Journal of Pathology, 158(5), 1723-1731.
Wang, G., Lai, F.M., Lai, K.B., Chow, K.M., Li, K.T. and Szeto, C.C. (2007) Messenger RNA expression of podocyte-associated molecules in the urinary sediment of patients with diabetic nephropathy. Nephron Clinical Practice, 106(4), c169-179.
Wang, G., Lai, F.M., Kwan, B.C., Lai, K.B., Chow, K.M., Li, P.K. and Szeto, C.C. (2009) Podocyte loss in human hypertensive nephrosclerosis. American Journal of Hypertension, 22(3), 300-306.
Vogelmann, S.U., Nelson, W.J., Myers, B.D. and Lemley, K.V. (2003) Urinary excretion of viable podocytes in health and renal disease. American Journal of Physiology Renal Physiology, 285(1), F40-48.
Ruotsalainen, V., Ljungberg, P., Wartiovaara, J., Lenkkeri, U., Kestila, M., Jalanko, H., Holmberg, C. and Tryg- gvason, K. (1999) Nephrin is specifically located at the slit diaphragm of glomerular podocytes. Proceedings of the National Academy of Sciences, USA, 96(14), 7962- 7967.
Jalanko, H. (2003) Pathogenesis of proteinuria: Lessons learned from nephrin and podocin. Pediatric Nephrology, 18(6), 487-491.