Novel oral plasminogen activator inhibitor ‑1 inhibitor TM5275 attenuates hepatic fibrosis under metabolic syndrome via suppression of activated hepatic stellate cells in rats.

Novel oral plasminogen activator inhibitor‑1 inhibitor TM5275 attenuates hepatic fibrosis under metabolic syndrome via suppression of activated hepatic stellate cells in rats. Mol Med Rep. 2020 Jul 28;: Authors: Noguchi R, Kaji K, Namisaki T, Moriya K, Kawaratani H, Kitade M, Takaya H, Aihara Y, Douhara A, Asada K, Nishimura N, Miyata T, Yoshiji H Abstract An orally bioavailable small molecule inhibitor of plasminogen activator inhibitor‑1 (PAI‑1) is currently being clinically assessed as a novel antithrombotic agent. Although PAI‑1 is known to serve a key role in the pathogenesis of metabolic syndrome (MetS) including nonalcoholic steatohepatitis (NASH), the pharmacological action of an oral PAI‑1 inhibitor against the development of MetS‑related liver fibrosis remains unclear. The current study was designed to explicate the effect of TM5275, an oral PAI‑1 inhibitor, on MetS‑related hepatic fibrogenesis. The in vivo antifibrotic effect of orally administered TM5275 was investigated in two different rat MetS models. Fischer 344 rats received a choline‑deficient L‑amino‑acid‑defined diet for 12 weeks to induce steatohepatitis with development of severe hepatic fibrosis. Otsuka Long‑Evans Tokushima Fatty rats, used to model congenital diabetes, underwent intraperitoneal injection of porcine serum for 6 weeks to induce hepatic fibrosis under diabetic conditions. In each experimental model, TM5275 markedly am...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research