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

Virginie Ory; Qingfeng Fan; Nabila Hamdaoui; Shao-Yu Zhang; Dominique Desvaux; Vincent Audard; Marina Candelier; Laure-Helene Noel; Philippe Lang; Georges Guellaën; Andre Pawlak; Djillali Sahali

doi:10.1016/j.ajpath.2012.02.008

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

Virginie Ory ¹ Qingfeng Fan ¹ Nabila Hamdaoui ¹ Shao-Yu Zhang ¹ Dominique Desvaux ^{1, 2} Vincent Audard ¹ Marina Candelier ¹ Laure-Helene Noel ^{3, 4} Philippe Lang ^{1, 5, 6} Georges Guellaën ¹ Andre Pawlak ^{1, 5} Djillali Sahali ^{1, 5, 6, *}

* Auteur correspondant

1 IMRB - Institut Mondor de Recherche Biomédicale

2 Service d'histologie

3 UM3 (UMR 8104 / U1016) - Institut Cochin

4 Service d'anatomie pathologique [CHU Necker]

5 Service de néphrologie et transplantation

6 Institut francilien de recheche en nephrologie et transplantation

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.

Type de document :

Article dans une revue

American Journal of Pathology, American Society for Investigative Pathology, 2012, 180 (6), pp.2284-92. 〈10.1016/j.ajpath.2012.02.008〉

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire

Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00717184
Contributeur : Georges Guellaen <>
Soumis le : jeudi 12 juillet 2012 - 10:54:43
Dernière modification le : jeudi 11 janvier 2018 - 06:23:10
Document(s) archivé(s) le : samedi 13 octobre 2012 - 02:21:43

AJP11-1939T_1.pdf

Fichiers produits par l'(les) auteur(s)

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

Fichier

Identifiants

Collections

Citation

Exporter

Métriques

426

178

Contact

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

Fichier

Identifiants

Collections

Citation

Exporter

Partager

Métriques

426

178

Contact