Journal
EXPERIMENTAL CELL RESEARCH
Volume 407, Issue 2, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112828
Keywords
Hepatic fibrosis; PM2.5; miR-411; Drp1; Mitophagy; Hepatic stellate cell
Categories
Funding
- National Natural Science Foundation of China [21906061]
Ask authors/readers for more resources
The study found that PM2.5 induced HSC proliferation and fibrosis by increasing the levels of ACTA2, Collagen 1, TIMP1, and TGF-beta 1. PM2.5 also reduced miR-411 expression, leading to mitochondrial dynamics dysfunction, and promoted mitophagy in HSCs. Additionally, miR-411 played a regulatory role in PM2.5-induced mitophagy by targeting Drp1.
Background: Particulate matter <= 2.5 mu m (PM2.5) is a type of environmental agent associated with air pollution, which induces hepatic fibrosis. However, the function and mechanism of PM2.5 on hepatic stellate cell (HSC) proliferation and fibrosis remain largely unknown. Methods: Human HSC line (LX-2) and murine HSCs were exposed to various doses of PM2.5. microRNA (miR)-411 expression was detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation, fibrosis, mitochondrial dynamics dysfunction and mitophagy were determined via cell counting kit-8 (CCK-8), qRT-PCR, Western blotting and immunofluorescence. Results: PM2.5 facilitated HSC proliferation and fibrosis via increasing the levels of ACTA2, Collagen 1, TIMP1 and TGF-beta 1. PM2.5 reduced miR-411 expression, and contributed to mitochondrial dynamics dysfunction via increasing Drp1 and decreasing OPA1, TOM20 and PGC-1 alpha levels. PM2.5 promoted mitophagy by upregulating the levels of Beclin-1, LC3II/I, PINK1 and Parkin. miR-411 overexpression or autophagy blockage using 3-methyladenine (3-MA) relieved PM2.5-mediated cell proliferation and fibrosis-associated factor expression in HSCs. Drp1 was targeted by miR-411. miR-411 mitigated PM2.5-induced mitophagy via targeting Drp1. Drp1 overexpression abolished the inhibitory role of miR-411 in cell proliferation and fibrosis-associated factor levels in HSCs. Conclusion: PM2.5 induced HSC activation and fibrosis via promoting Drp1-mediated mitophagy by decreasing miR-411, thereby causing liver fibrosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available