title: Upregulation of nuclear factor-related kappa B suggests a disorder of transcriptional regulation in minimal change nephrotic syndrome.
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 the first time that NFRKB may be involved in the disorders of transcriptional regulation commonly observed in MCNS relapse.
authors.affiliation: INSERM U 955, Créteil, France. vincent.audard@hmn.aphp.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: Audard
authors.forename: André
authors.initials: A
authors.lastname: Pawlak
authors.forename: Marina
authors.initials: M
authors.lastname: Candelier
authors.forename: Philippe
authors.initials: P
authors.lastname: Lang
authors.forename: Djillali
authors.initials: D
authors.lastname: Sahali
mesh_terms: D000293:Adolescent; D000328:Adult; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D012008:Recurrence; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C072725:NFRKB protein, human