Valproate hampers podocyte acquisition of immune phenotypes via intercepting the GSK3 β facilitated NFkB activation.

Valproate hampers podocyte acquisition of immune phenotypes via intercepting the GSK3β facilitated NFkB activation.
Oncotarget. 2017 Oct 24;8(51):88332-88344
Authors: Wang P, Zhou S, Ge Y, Lu M, Liu Z, Gong R
Abstract
Glomerular podocytes are able to transdifferentiate under disease conditions, acquire de novo immune phenotypes and behave as immunocompetent cells, like phagocytes or antigen-presenting cells. Upon stimulation with lipopolysaccharide (LPS), a prototypical pathogen-associated molecular pattern, podocytes demonstrated de novo expression of a variety of NFkB-dependent immune molecules that are pivotal for immune response, including major histocompatibility complex (MHC) class II, costimulatory molecule CD80, lysosomal protease cathepsin L as well as CC chemokine ligand 2 and 5, ultimately resulting in podocyte dysfunction, characterized by cellular shrinkage, a spindle-like or asterlike cell shape and impairment of actin cytoskeleton integrity. The LPS-elicited podocyte phenotypic changes were concurrent with nuclear factor (NF) kB phosphorylation, which was associated with glycogen synthase kinase (GSK) 3β overactivity, marked by a diminished inhibitory phosphorylation of GSK3β. In contrast, valproate, an anticonvulsant and mood stabilizer, offset GSK3β overactivity in LPS-injured podocytes and mitigated NFkB activation and podocyte acquisition of immune phenotypes as well as the ensuing cytopathic changes, podocyte ...

Source: Oncotarget - November 29, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research