Published in:
10-08-2022 | Hypertension | Original Article
Downregulation of miR-20b-5p Contributes to the Progression of Liver Fibrosis via the STAT3 Signaling Pathway In Vivo and In Vitro
Published in: Digestive Diseases and Sciences | Issue 2/2023
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Background
Activated hepatic stellate cells (HSCs) are primarily involved in liver fibrosis and portal hypertension (PHT). We aimed to investigate the effect of miR-20b-5p on HSCs, liver fibrosis, and PHT.
Methods
MiR-20b-5p expression in HSCs and in mouse liver fibrosis was determined by qPCR. Further, the effects of miR-20b-5p mimic on HSCs migration, proliferation, and apoptosis were investigated in vitro. A dual-luciferase reporter assay was performed to confirm the direct interaction between miR-20b-5p and STAT3. In vivo, mouse liver fibrosis was established by common bile duct ligation and intervened by agomiR-20b-5p. Sirius red staining and hydroxyproline content were used to evaluate collagen deposition. The α-SMA expression in the liver was detected by IHC and Western blotting. The STAT3 signaling pathway and its downregulated cytokines as well as portal pressure and angiogenesis were explored.
Results
MiR-20b-5p was significantly downregulated during HSCs activation and in mouse liver fibrosis. The functional analyses demonstrated that miR-20b-5p inhibited cell proliferation, activation, and promoted apoptosis in HSCs in vitro. Moreover, miR-20b-5p regulated STAT3 expression by binding to the 3'UTR of its miRNA directly. Overexpression of miR-20b-5p facilitated HSC activation and proliferation by inhibiting the STAT3 signaling pathway. MiR-20b-5p overexpression suppressed the STAT3 and its downstream cytokines and ameliorated liver fibrosis in mice. The intra- and inter-hepatic angiogenesis were also effectively inhibited. The inhibition of liver fibrosis and neoangiogenesis contributed to the decrease of portal pressure.
Conclusions
MiR-20b-5p plays an important role in the fibrosis and angiogenesis of liver fibrosis by targeting the STAT3 signaling pathway.