期刊
SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41598-020-76148-5
关键词
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资金
- NIH [K08 AA021404-01]
- NIAAA [R03 AA027335-01]
Exaggerated transforming growth factor-beta 1 (TGF beta 1) expression worsens fibroproliferation following bleomycin-induced lung injury in alcohol-fed mice. MicroRNA (miR)-1946a is predicted to bind to the TGF beta 1 3' untranslated region (UTR), thereby inhibiting its transcription. We hypothesize that alcohol suppresses miR-1946a and induces TGF beta 1. Primary murine lung fibroblasts (PLFs) were cultured +/- alcohol, miR-1946a mimic or inhibitor, and TGF beta 1 signaling inhibitors. miR-1946a was analyzed after alcohol treatment in vitro and in vivo. TGF beta 1 expression and TGF beta 1 3'UTR-luciferase activity was quantified. We showed that alcohol suppressed miR-1946a in the alcohol-fed mouse lungs and PLFs. MiR-1946a inhibitor increased TGF beta 1 expression in the fibroblast. MiR-1946a mimic treatment suppressed TGF beta 1 gene expression and TGF beta 1 3'UTR activity. Overexpression of miR1946a inhibited alcohol-induced TGF beta 1 gene and protein expression as well as alcohol-induced TGF beta 1 and a-smooth muscle actin (SMA) protein expression in PLFs. In conclusion, miR-1946a modulates TGF beta 1 expression through direct interaction with TGF beta 1 3'UTR. These findings identify a novel mechanism by which alcohol induces TGF beta 1 in the lung.
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