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c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes.

Abstract : The mechanisms of podocyte disorders in cases of idiopathic nephrotic syndrome (INS) are complex and remain incompletely elucidated. The abnormal regulation of NF-κB may play a key role in the pathophysiology of these podocyte diseases, but at present, NF-κB has not been thoroughly investigated. In this study, we report that induction of c-mip in podocytes of patients with INS is associated with a down-regulation of RelA, a potent antiapoptotic factor that belongs to the NF-κB family. Overexpression of c-mip in differentiated podocytes promotes apoptosis by inducing caspase-3 activity and up-regulating the proapoptotic protein Bax, whereas the overall levels of the antiapoptotic protein Bcl-2 was concomitantly decreased. The associated overexpression of RelA prevented the proapoptotic effects of c-mip. In addition, the targeted induction of c-mip in podocytes in vivo inhibited the expression of the RelA protein and increased the Bax/Bcl-2 ratio. The expression of both c-mip and active caspase-3 increased in focal and segmental glomerulosclerosis biopsies, and both proteins displayed a close spatial relationship. These results suggest that alterations in NF-κB activity might result from the up-regulation of c-mip and are likely to contribute to podocyte disorders in cases of INS.
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https://www.hal.inserm.fr/inserm-00717184
Contributor : Georges Guellaen <>
Submitted on : Thursday, July 12, 2012 - 10:54:43 AM
Last modification on : Wednesday, August 19, 2020 - 11:16:37 AM
Long-term archiving on: : Saturday, October 13, 2012 - 2:21:43 AM

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Virginie Ory, Qingfeng Fan, Nabila Hamdaoui, Shao-Yu Zhang, Dominique Desvaux, et al.. c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes.. American Journal of Pathology, American Society for Investigative Pathology, 2012, 180 (6), pp.2284-92. ⟨10.1016/j.ajpath.2012.02.008⟩. ⟨inserm-00717184⟩

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