Journal
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Volume 50, Issue 6, Pages -Publisher
WILEY
DOI: 10.1111/eci.13243
Keywords
hepatic fibrosis; HSC activation; lncRNA LOC102551149; miR-23a-5p; PI3K; Akt; PTEN
Funding
- Natural Science Foundation of Inner Mongolia Autonomous Region [2017MS0831, 2018LH08032, 2019MS08110]
- National Natural Science Foundation of China [81550047, 81760748]
- Major Science Foundation of Affiliated Hospital of Inner Mongolia Medical University [NYFY ZD 010]
- Inner Mongolia Autonomous Region Prairie excellenceProject
- Western Light Young Scholars Program of the Chinese Academy of Sciences
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Background Hepatic fibrosis is a worldwide incurable disease; due to the complex and unclear mechanism, there lack the effective therapeutic targets. However, the mechanism of miR-23a-5p underling this pathological process is largely not clear. The purpose of this study was to investigate the role of miR-23a-5p in hepatic fibrosis and HSC activation. Methods The content of miR-23a-5p in hepatic fibrosis induced by N-nitrosodimethylamine (NDMA) and HSC activation induced by platelet-derived growth factor (PDGF) was detected by qRT-PCR. H&E staining, Masson staining and Shear wave electrography (SWE) were used to detect the degree of hepatic fibrosis. Immunohistochemistry staining, qRT-PCR and Western blot detect the related markers of liver fibrosis or HSC activation, as well as the related pathway genes and proteins. Dual-luciferase reporter system verifies the interaction between miR-23a-5p with PTEN or miR-23a-5p with lncRNA LOC102551149 in HSC-T6. siRNA and miRNA mimic transfer to HSC-T6 to detect the function of lncRNA LOC102551149 and miR-23a-5p on HSC activation. Results After hepatic fibrosis and HSC activation happened, the expression of miR-23a-5p was up-regulated, whereas anti-miR-23a-5p can alleviate hepatic fibrosis and HSC activation. Further research shows miR-23a-5p can target PTEN and degrade it, causing activation of PI3K/Akt/mTOR/Snail pathway. lncRNA LOC102551149 can be used as a competition endogenous RNA (ceRNA) targeting miR-23a-5p through base pairing, and siRNA LOC102551149 or exogenous miR-23a-5p can induce HSC activation through PI3K/Akt/mTOR/Snail pathway. Conclusion We demonstrate mechanism pathway of miR-23a-5p on hepatic fibrosis and HSC activation, which may develop a therapeutic target for hepatic fibrosis.
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