Nephrin deficiency activates NF-kappaB and promotes glomerular injury

S Hussain, L Romio, MA Saleem, PW Mathieson, M Serrano, J Moscat, M Diaz-Meco, P Scambler, A Koziell

Research output: Contribution to journalArticle (Academic Journal)peer-review

50 Citations (Scopus)


Increasing evidence implicates activation of NF-kappaB in a variety of glomerular diseases, but the mechanisms involved are unknown. Here, upregulation of NF-kappaB in the podocytes of transgenic mice resulted in glomerulosclerosis and proteinuria. Absence of the podocyte protein nephrin resulted in NF-kappaB activation, suggesting that nephrin negatively regulates the NF-kappaB pathway. Signal transduction assays supported a functional relationship between nephrin and NF-kappaB and suggested the involvement of atypical protein kinase C (aPKCzeta/lambda/iota) as an intermediary. We propose that disruption of the slit diaphragm leads to activation of NF-kappaB; subsequent upregulation of NF-kappaB-driven genes results in glomerular damage mediated by NF-kappaB-dependent pathways. In summary, nephrin may normally limit NF-kappaB activity in the podocyte, suggesting a mechanism by which it might discourage the evolution of glomerular disease.
Translated title of the contributionNephrin deficiency activates NF-kappaB and promotes glomerular injury
Original languageEnglish
Pages (from-to)1733 - 1743
Number of pages11
JournalJournal of the American Society of Nephrology
Publication statusPublished - Aug 2009

Bibliographical note

Other: Epub 2009 Jun 4

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