MicroRNA-26a-CD36 signaling pathway: Pivotal role in lipid accumulation in hepatocytes induced by PM2.5 liposoluble extracts
2019
Ding, Dongxiao | Ye, Guozhu | Lin, Yi | Lu, Yanyang | Zhang, Han | Zhang, Xu | Hong, Zhenyu | Huang, Qiansheng | Chi, Yulang | Chen, Jinsheng | Dong, Sijun
Exposure to ambient particular matters (PM) has been associated with the development of non-alcoholic fatty liver disease (NAFLD), but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study aimed to explore the role of miRNA-mRNA regulation underlying abnormal lipid metabolism triggered by PM₂.₅liposoluble extracts. We confirmed that 72-h exposure to liposoluble extracts of PM₂.₅ from Nanjing at 25 μg/cm² induced lipid accumulation in HepG2 cells by promoting uptake of free fatty acids (FFAs). Notably, lipid accumulation induced by PM₂.₅ liposoluble extracts was associated with decreased expression of miR-26a and consequent upregulation of fatty acid translocase (FAT, also known as CD36). Using gain- and loss-of-function assays, we demonstrated that miR-26a negatively regulated CD36 to mediate lipid accumulation in HepG2 cells. We further confirmed that miR-26a directly acted on the 3′ untranslated region (3′UTR) of CD36. Furthermore, overexpression of miR-26a abolished steatosis in HepG2 cells treated with PM₂.₅ liposoluble extracts by suppressing CD36. In addition, we demonstrated that PM₂.₅ liposoluble extracts caused inflammation in HepG2 cells by raising p65 phosphorylation, thereby fuelling the transition from simple non-alcoholic fatty liver to non-alcoholic steatohepatitis. In conclusion, this study demonstrated a novel mechanism by which miR-26a-CD36 pathway mediated lipid accumulation induced by PM₂.₅ liposoluble extracts in hepatocytes. Lipid accumulation and inflammation induced by PM₂.₅ liposoluble extracts implied the potential role of PM₂.₅ in developing NAFLD.
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