| First Author | Hussain S | Year | 2009 |
| Journal | J Am Soc Nephrol | Volume | 20 |
| Issue | 8 | Pages | 1733-43 |
| PubMed ID | 19497968 | Mgi Jnum | J:164621 |
| Mgi Id | MGI:4834735 | Doi | 10.1681/ASN.2008111219 |
| Citation | Hussain S, et al. (2009) Nephrin deficiency activates NF-kappaB and promotes glomerular injury. J Am Soc Nephrol 20(8):1733-43 |
| abstractText | 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. |
