Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 107, Issue -, Pages 318-328Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2017.07.014
Keywords
Collagen synthese; Dioscin; ITGA5 inhibitor; SILAC method
Categories
Funding
- National Natural Science Foundation of China [81274195]
- Project of Liaoning BaiQianWan Talents Program [2015-65]
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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, Coll al, Coll a2, Col2al, 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 against hepatic fibrosis. (C) 2017 Elsevier Ltd. All rights reserved.
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