MicroRNA-26a-CD36 signaling pathway: Pivotal role in lipid accumulation in hepatocytes induced by PM liposoluble extracts.

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 PMliposoluble extracts. We confirmed that 72-h exposure to liposoluble extracts of PM from Nanjing at 25 μg/cm induced lipid accumulation in HepG2 cells by promoting uptake of free fatty acids (FFAs). Notably, lipid accumulation induced by PM 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 PM liposoluble extracts by suppressing CD36. In addition, we demonstrated that PM 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 PM liposoluble extracts in hepatocytes. Lipid accumulation and inflammation induced by PM liposoluble extracts implied the potential role of PM in developing NAFLD.