期刊
ENVIRONMENTAL POLLUTION
卷 248, 期 -, 页码 269-278出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.envpol.2019.01.112
关键词
Liposoluble extracts of PM2.5; MicroRNA-26a (miR-26a); Fatty acid translocase (FAT, also known as CD36); Lipid accumulation; Inflammation
资金
- National Natural Science Foundation of China [41390240, 21677140, 21477124]
- CAS-JSPS Collaboration Project [132C35KYSB20180006]
- Youth Innovation Promotion Association, CAS [2017349]
- Chinese Academy of Sciences Interdisciplinary Innovation Team Project
- National Key Research & Development Program [2016YFC02005, 2016YFE0112200]
- Natural Science Foundation of Fujian, China [2017J01028]
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 PM(2.5)liposoluble extracts. We confirmed that 72-h exposure to liposoluble extracts of PM25 from Nanjing at 25 mu g/cm(2) 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. (C) 2019 Elsevier Ltd. All rights reserved.
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