Sja-Let-7 Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in a Mouse Model via Col1α2

文献类型： 外文期刊

第一作者： Zhong, Haoran

作者： Zhong, Haoran;Dong, Bowen;Zhu, Danlin;Li, Hao;Lu, Ke;Fu, Zhiqiang;Liu, Jinming;Jin, Yamei;Zhong, Haoran;Dong, Bowen;Zhu, Danlin;Li, Hao;Lu, Ke;Fu, Zhiqiang;Liu, Jinming;Jin, Yamei

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关键词： liver fibrosis; hepatic stellate cell; sja-let-7; Col1 alpha 2; TGF-beta/Smad signaling pathway

期刊名称：BIOLOGY-BASEL （ 影响因子：4.2； 五年影响因子：4.4 ）

ISSN：

年卷期： 2023 年 12 卷 12 期

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收录情况： SCI

摘要： Liver fibrosis (LF) is a chronic progressive disease with no definitive treatment. The aim of this study was to assess helminth-derived molecules as potential therapeutic targets to prevent or reverse LF. A mouse model of carbon tetrachloride (CCL4)-induced LF was established and sja-let-7 was overexpressed by treatment with a miRNA agomir once per week. After four weeks, serum biochemistry, hepatic hydroxyproline content measurements, liver histology, mRNA expression profiling of fibrotic markers, the dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH) were performed. Administration of the sja-let-7 agomir markedly ameliorated hepatosplenomegaly and reduced the liver hydroxyproline content. Liver histological analysis showed significant reductions in collagen deposition in the sja-let-7 agomir-treated mice. Additionally, the mRNA levels of both pro-fibrotic markers and pro-inflammatory cytokines were diminished after treatment. Furthermore, the dual-luciferase reporter assay and FISH identified the alpha 2 chain of collagen type 1 (Col1 alpha 2) as the direct target of sja-let-7. Accordingly, the progression of LF was attenuated by targeting Col1 alpha 2 and the TGF-beta/Smad signaling pathway.

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