a new antifibrotic target of ac-sdkp inhibition of myofibroblast differentiation in rat lung with silicosis新的ac-sdkp antifibrotic目标抑制myofibroblast分化与矽肺大鼠肺.pdfVIP

A New Antifibrotic Target of Ac-SDKP: Inhibition of Myofibroblast Differentiation in Rat Lung with Silicosis 1 1,2 2 2 2 2 2 1 Hong Xu , Fang Yang *, Ying Sun , Yuan Yuan , Hua Cheng , Zhongqiu Wei , Shuyu Li , Tan Cheng , Darrell Brann3, Ruimin Wang2 1 Department of Pathology, Hebei Medical University, Shi Jiazhuang, China, 2 Medical Research Center, Hebei United University, Tangshan, China, 3 Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, Georgia, United States of America Abstract Background: Myofibroblast differentiation, characterized by a-smooth muscle actin (a-SMA) expression, is a key process in organ fibrosis, and is induced by TGF-b. Here we examined whether an anti-fibrotic agent, N-acetyl-seryl-aspartyl- lysylproline (Ac-SDKP), can regulate induction of TGF-b signaling and myofibroblast differentiation as a potential key component of its anti-fibrotic mechanism in vivo and in vitro. Methodology/Principal Findings: Rat pulmonary fibroblasts were cultured in vitro and divided to 4 groups 1) control; 2) TGF- b1; 3) TGF-b1+ LY364947; 4) TGF-b1+Ac-SDKP. For in vivo studies, six groups of animals were utilized 1) control 4w; 2) silicotic 4w; 3) control 8w; 4) silicotic 8w; 5) Ac-SDKP post-treatment; 6)Ac-SDKP pre-treatment. SiO2 powders were douched in the trachea of rat to make the silicotic model. Myofibroblast differentiation was measured by examining expression of a- SMA, as well as expression of serum response factor (SRF), a key regulator of myofibroblast differentiation. The expressions of collagen, TGF-b1 and RAS signaling were also assessed. The results revealed that TGF-b1 strongly induced myofibroblast differ