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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/F945    most recent 00423.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Lai, K. N. Articles by Tang, S. C. W. Search for Related Content PubMed PubMed Citation Articles by Lai, K. N. Articles by Tang, S. C. W.

Activation of podocytes by mesangial-derived TNF-: glomerulo-podocytic communication in IgA nephropathy

¹Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong; ²Academic Renal Unit, University of Bristol, Bristol, United Kingdom; and ³Department of Pathology, Chinese University of Hong Kong, Hong Kong

Submitted 10 September 2007 ; accepted in final form 29 January 2008

We have previously documented that human mesangial cell (HMC)-derived TNF- is an important mediator involved in the glomerulo-tubular communication in the development of interstitial damage in IgA nephropathy (IgAN). With the strategic position of podocytes, we further examined the role of mesangial cells in the activation of podocytes in IgAN. There was no binding of IgA from patients with IgAN to podocytes. Podocytes cultured with IgA from patients with IgAN did not induce the release of growth factors or cytokines. Furthermore, podocytes did not express mRNA of known IgA receptors. In contrast, IgA-conditioned medium (IgA-HMC medium) prepared by culturing HMC with IgA from patients with IgAN for 48 h significantly increased the gene expression and protein synthesis of TNF- by podocytes with a 17-fold concentration above that of IgA-HMC medium. The upregulation of TNF- expression by podocyte was only abolished by a neutralizing antibody against TNF- but not by other antibodies. Exogenous TNF- upregulated the synthesis of TNF- by podocytes in an autocrine fashion. IgA-HMC medium prepared with IgA from patients with IgAN also significantly upregulated the expression of both TNF- receptor 1 and 2 in podocytes. Our in vitro finding suggests podocytes may play a contributory role in the development of interstitial damage in IgAN by amplifying the activation of tubular epithelial cells with enhanced TNF- synthesis after inflammatory changes of HMC.

tumor necrosis factor-; mesangial cell; tubulointerstitial injury

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