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The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1
Author(s) -
Han Yantao,
Jiang Qixiao,
Wang Yu,
Li Wenqian,
Geng Min,
Han Zhiwu,
Chen Xuehong
Publication year - 2017
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10838
Subject(s) - cell growth , chemistry , apoptosis , oleanolic acid , vascular smooth muscle , cell , fibroblast growth factor , endocrinology , medicine , biology , biochemistry , receptor , alternative medicine , pathology , smooth muscle
Vascular smooth muscle cell (VSMC) proliferation is a major contributor to atherosclerosis. This study investigated the inhibitory effects of oleanolic acid (OA) against oxidized low‐density lipoprotein (ox‐LDL)‐induced VSMC proliferation in A7r5 cells and explored underlying molecular mechanism. The cell proliferation was quantified with cell counting kit‐8 (CCK‐8), in which ox‐LDL significantly increased A7r5 cells proliferation, while OA pretreatment effectively alleviated such changes without inducing overt cytotoxicity, as indicated by lactate dehydrogenase (LDH) assay. Quantitative real‐time RT‐PCR (qRT‐PCR) and Western blotting revealed increased UCP2 and FGF‐2 expression levels as well as decreased p53 and TSP‐1 expression levels in A7r5 cells following ox‐LDL exposure, while OA pretreatment reversed such changes. Furthermore, inhibiting UCP2 with genipin remarkably reversed the changes in the expression levels of FGF‐2, p53, and TSP‐1 induced by ox‐LDL exposure; silencing FGF‐2 with siRNA did not significantly change the expression levels of UCP2 but effectively reversed the changes in the expression levels of p53 and TSP‐1, and activation of p53 with PRIMA‐1 only significantly affected the changes in the expression levels of TSP‐1, but not in UCP2 or FGF‐2, suggesting a UCP‐2/FGF‐2/p53/TSP‐1 signaling in A7r5 cells response to ox‐LDL exposure. Additionally, co‐treatment of OA and genipin exhibited similar effects to the expression levels of UCP2, FGF‐2, p53, and TSP‐1 as OA or genipin solo treatment in ox‐LDL‐exposed A7r5 cells, suggesting the involvement of UCP‐2/FGF‐2/p53/TSP‐1 in the mechanism of OA. In conclusion, OA inhibits ox‐LDL‐induced VSMC proliferation in A7r5 cells, the mechanism involves the changes in UCP‐2/FGF‐2/p53/TSP‐1.