Nephrin Deficiency Activates NF-kappa B and Promotes Glomerular Injury

作者：Hussain Sagair; Romio Leile; Saleem Moin; Mathieson Peter; Serrano Manuel; Moscat Jorge; Diaz Meco Maria; Scambler Peter; Koziell Ania^*

来源：Journal of the American Society of Nephrology, 2009, 20(8): 1733-1743.

DOI：10.1681/ASN.2008111219

Increasing evidence implicates activation of NF-kappa B in a variety of glomerular diseases, but the mechanisms involved are unknown. Here, upregulation of NF-kappa B in the podocytes of transgenic mice resulted in glomerulosclerosis and proteinuria. Absence of the podocyte protein nephrin resulted in NF-kappa B activation, suggesting that nephrin negatively regulates the NF-kappa B pathway. Signal transduction assays supported a functional relationship between nephrin and NF-kappa B and suggested the involvement of atypical protein kinase C (aPKC zeta/lambda/iota) as an intermediary. We propose that disruption of the slit diaphragm leads to activation of NF-kappa B; subsequent upregulation of NF-kappa B-driven genes results in glomerular damage mediated by NF-kappa B-dependent pathways. In summary, nephrin may normally limit NF-kappa B activity in the podocyte, suggesting a mechanism by which it might discourage the evolution of glomerular disease.

• 出版日期2009-8