Hepatology international · 2022
miR-488-5p mitigates hepatic stellate cell activation and hepatic fibrosis via suppressing TET3 expression.
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Qiu Jiannan, Wu Shasha, Wang Peng, Zhou Yan, Wang Zhongxia, Sun Yong, Jiang Chunping
Аннотация
BACKGROUND AND AIMS: Numerous studies have demonstrated that hepatic fibrosis, a progressive condition as an endpoint of multiple chronic hepatic diseases, is largely characterized with the extensive activation of hepatic stellate cells (HSCs). The precise effect of miR-488-5p in HSCs during hepatic fibrosis has not been elucidated.
METHODS: In our study, qRT-PCR was applied to assess the level of miR-488-5p in activated HSCs stimulated by TGF-β1. We built murine liver fibrosis models with carbon tetrachloride (CCl4), high-fat diet (HFD) and bile duct ligation (BDL). In vitro, the effects of miR-488-5p in HSCs were examined through cell proliferation assay and apoptosis. Luciferase reporter assay was applied to identify the underlying target of miR-488-5p. In vivo, the effects of miR-488-5p were explored through mouse liver fibrosis models.
RESULTS: The reduction of miR-488-5p in the activated HSCs induced by TGF-β1 and three mouse hepatic fibrosis models were identified. The in vitro functional experimentations verified that miR-488-5p restrained expression of fibrosis-related markers and proliferative capacity in HSCs. Mechanically, we identified that miR-488-5p inhibited tet methylcytosine dioxygenase 3 (TET3) expression via straightly binding onto the 3' UTR of its mRNA, which sequentially restrained the TGF-β/Smad2/3 pathway. TET3 inhibition induced by the overexpression of miR-488-5p reduced extracellular matrix deposition, which contributed to mitigating mouse liver fibrosis.
CONCLUSION: We highlight that miR-488-5p restrains the activation of HSCs and hepatic fibrosis via targeting TET3 which is involved in the TGF-β/Smad2/3 signaling pathway. Collectively, miR-488-5p is identified as a potential therapeutic target for hepatic fibrosis.
METHODS: In our study, qRT-PCR was applied to assess the level of miR-488-5p in activated HSCs stimulated by TGF-β1. We built murine liver fibrosis models with carbon tetrachloride (CCl4), high-fat diet (HFD) and bile duct ligation (BDL). In vitro, the effects of miR-488-5p in HSCs were examined through cell proliferation assay and apoptosis. Luciferase reporter assay was applied to identify the underlying target of miR-488-5p. In vivo, the effects of miR-488-5p were explored through mouse liver fibrosis models.
RESULTS: The reduction of miR-488-5p in the activated HSCs induced by TGF-β1 and three mouse hepatic fibrosis models were identified. The in vitro functional experimentations verified that miR-488-5p restrained expression of fibrosis-related markers and proliferative capacity in HSCs. Mechanically, we identified that miR-488-5p inhibited tet methylcytosine dioxygenase 3 (TET3) expression via straightly binding onto the 3' UTR of its mRNA, which sequentially restrained the TGF-β/Smad2/3 pathway. TET3 inhibition induced by the overexpression of miR-488-5p reduced extracellular matrix deposition, which contributed to mitigating mouse liver fibrosis.
CONCLUSION: We highlight that miR-488-5p restrains the activation of HSCs and hepatic fibrosis via targeting TET3 which is involved in the TGF-β/Smad2/3 signaling pathway. Collectively, miR-488-5p is identified as a potential therapeutic target for hepatic fibrosis.