Brain natriuretic peptide mitigates TIMP2 induction and reinstates extracellular matrix catabolic activity via GSK3β inhibition in glomerular podocytes exposed to a profibrogenic milieu.

ABSTRACT: Brain natriuretic peptide (BNP) has a demonstrable anti-fibrotic effect on diverse organ systems, including the kidney. To understand the molecular mechanism underlying this renoprotective effect, the efficacy of BNP was examined in an in vitro model of glomerular sclerosis by exposing glomerular podocytes to transforming growth factor (TGF)β1-containing media that recapitulates the profibrogenic milieu in chronic glomerular disease. BNP mitigates extracellular matrix (ECM) accumulation in TGFβ1-treated podocytes, as evidenced by Sirius red assay and staining, concomitant with a restoration of the ECM catabolizing activity, as assessed by pulse chase analysis. This effect was in parallel with a mitigating effect on TGFβ1-elicited overexpression of tissue inhibitor of metalloproteina

SUBMITTER: Guo Q 

PROVIDER: S-EPMC6413260 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature