c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes. - Archive ouverte HAL Access content directly
Journal Articles American Journal of Pathology Year : 2012

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

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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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Dates and versions

inserm-00717184 , version 1 (12-07-2012)

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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, 2012, 180 (6), pp.2284-92. ⟨10.1016/j.ajpath.2012.02.008⟩. ⟨inserm-00717184⟩
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