upregulation of nuclear factor-related kappa b suggests a disorder of transcriptional regulation in minimal change nephrotic syndromeupregulation核factor-relatedκb显示转录调控的紊乱微小病变性肾病综合症.pdfVIP

Upregulation of Nuclear Factor-Related Kappa B Suggests a Disorder of Transcriptional Regulation in Minimal Change Nephrotic Syndrome 1,2,3,4 . ´ 1,2. 1,2 1,2,3,4 1,2,3,4 Vincent Audard * , Andre Pawlak , Marina Candelier , Philippe Lang , Djillali Sahali ´ ´ ´ ´ ´ 1 INSERM U 955, Creteil, France, 2 Universite Paris-Est, Creteil, France, 3 AP-HP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Service de Nephrologie, Creteil, France, ´ 4 Institut Francilien de Recherche en Nephrologie et Transplantation, Henri Mondor Hospital, Creteil, France Abstract Immune mechanisms underlying the pathophysiology of idiopathic nephrotic syndrome, the most frequent glomerular disease in children, are believed to involve a systemic disorder of T cell function and cell mediated immunity. How these perturbations take place remains unclear. We report here that NFRKB, a member of the chromatin remodeling complex, is upregulated in MCNS relapse, mainly in CD4+T cells and B cells and undergo post-translational modifications including sumoylation. We showed that NFRKB was highly expressed in nuclear compartment during the relapse, while it was restricted to cytoplasm in remission. NFRKB induced the activation of AP1 signaling pathway by upregulating the expression of c-jun. We showed that NFRKB promotes hypomethylation of genomic DNA, suggesting its implication in regulation of gene expression by enhancing the binding of transcription factors through chromatin remodeling. These results suggest for