PMID: identifiant
de la référence Pubmed : |
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 (22507836) |
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| titre : |
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c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes. |
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| auteur(s) : |
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Virginie Ory1, Qingfeng Fan1, Nabila Hamdaoui1, Shao-Yu Zhang1, Dominique Desvaux1, 2, Vincent Audard1, Marina Candelier1, Laure-Helene Noel3, 4, Philippe Lang1, 5, 6, Georges Guellaën1, Andre Pawlak1, 5, Djillali Sahali ( ) 1, 5, 6 |
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| laboratoire : |
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| résumé : |
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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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| domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0002-9440 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1016/j.ajpath.2012.02.008 |
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| journal : |
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| American Journal of Pathology (Am J Pathol) |
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American Society for Investigative Pathology (ASIP) |
| ISSN |
0002-9440 (eISSN : 1525-2191) |
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| Audience : |
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internationale |
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| date de publication : |
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06/2012 |
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date de publication
électronique : |
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14/04/2012 |
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| volume : |
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180 |
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| numéro : |
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6 |
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| page, identifiant, ... : |
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2284-92 |
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| Descripteur(s) MeSH : |
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Adult – Animals – Apoptosis – Carrier Proteins – Caspase 3 – Cell Line – Down-Regulation – Humans – In Situ Nick-End Labeling – Male – Mice – Transgenic – Microscopy – Confocal – NF-kappa B – Nephrotic Syndrome – Podocytes – Transcription Factor RelA – Up-Regulation |
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| contrat, financement : |
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This work was supported in part by an Avenir Program from INSERM, a grant from the French Kidney Foundation, Association pour l'Utilisation du Rein Artificiel (AURA), Assistance Publique des Hôpitaux de Paris (AP-HP, Programme hospitalier de recherche clinique) and a grant from the Fondation pour la Recherche Médicale (FRM). |
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