Dioscin, a potent ITGA5 inhibitor, reduces the synthesis of collagen against liver fibrosis: Insights from SILAC-based proteomics analysis.

Dioscin, a potent ITGA5 inhibitor, reduces the synthesis of collagen against liver fibrosis: Insights from SILAC-based proteomics analysis. Food Chem Toxicol. 2017 Jul 06;: Authors: Xu L, Yin L, Tao X, Qi Y, Han X, Xu Y, Song S, Li L, Sun P, Peng J Abstract Inhibiting collagen generation is one effective method to treat liver fibrosis. Dioscin showed protective effect against liver fibrosis in our previous studies, and in the present work, SILAC-based proteomics was employed to test the underlying mechanism. A total of 121 differentially expressed proteins caused by dioscin in LX-2 cells were found, and dioscin significantly decreased the expression levels of FN, FAK1, ITGA5, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, Col1a1, Col1a2, Col2a1, Col5a1, Col6a1, and increased 2ABB level in vivo and in vitro. Thus, we elucidated that dioscin specifically suppressed collagen synthesis through modulating PI3K/Akt pathway. In addition, we found that dioscin directly targeted with ITGA5 by molecular docking assay. SiRNA and overexpression transfection tests showed that ITGA5 siRNA plus dioscin slightly altered the effect of ITGA5 siRNA, and ITGA5 DNA transfection reversed the inhibitory effect of dioscin on collagen expressions via PI3K/Akt pathway. Our data explicated that dioscin should be considered as a novel and potent ITGA5 inhibitor to suppress collagen synthesis, which can also be developed as an effective food and healthcare product agains...
Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research