CG200745, a Novel HDAC Inhibitor, Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome.

ABSTRACT: Histone deacetylases have been a target of therapy for organ fibrosis. Here, we report the protective effect of CG200745 (CG), a novel histone deacetylase inhibitor, on tubulointerstitial fibrosis in Col4a3-/- mice, a murine model of Alport syndrome. Morphological analyses revealed CG treatment markedly alleviated kidney fibrosis in Col4a3-/- mice at the age of 7 weeks. CG prevented the activation of transforming growth factor β (TGFβ) and its downstream SMAD signaling in the kidney of Col4a3-/- mice. As critical upstream regulators of TGFβ signaling, immunoblotting of whole kidney lysate of Col4a3-/- mice reveled that intra-renal renin-angiotensin system (RAS) was activated with concurrent upregulation of inflammation and apoptosis, which were effectively suppressed by CG treatment. CG su

SUBMITTER: Suh SH 

PROVIDER: S-EPMC7073208 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature