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      저자 : Lai Thuy Linh (검색결과 1 건)

      • Irisin attenuates hepatic stellate cell activation and liver fibrosis in bile duct ligation mice model and improves mitochondrial dysfunction

        Lai Thuy Linh 강원대학교 대학원 2024 국내석사

        RANK : 233039

        Background: Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to discover the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods: In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor beta 1 (TGF-β1) which is a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 µg/kg/day) for 10 days. Results: In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and Sirt3. Additionally, irisin restored mitochondrial membrane potential and adenosine triphosphate production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion: Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis. Keywords: liver fibrosis, irisin, hepatic stellate cells, mitochondrial dysfunction, TGF-β1

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