Liver international : official journal of the International Association for the Study of the Liver · 2025
miR-210-3p Ameliorates Metabolic Dysfunction-Associated Steatohepatitis-Related Fibrosis by Targeting ISCU and Induces Ferroptosis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Dai Zixing, Sun Zhenhua, Chen Qingling, Li Yuwen, Sun Ye, Jiao Mengfan, Yin Xizhi, Liu Rui, Liang Hui, Zhu Chuanlong
Аннотация
BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH)-related fibrosis plays an important role in MASH prognosis; however, the underlying mechanism remains unknown. Here, we explored the involvement of miR-210-3p in MASH-associated fibrosis.
METHODS: We examined miR-210-3p expression in patients with MASH, with or without fibrosis using microarray analysis. miR-210-3p expression both in vivo and in vitro was validated using real-time quantitative reverse transcription PCR (RT-qPCR). Target genes and mechanisms were explored using western blotting, dual luciferase assay and immunofluorescence staining. Ferroptosis was assessed based on the levels of malondialdehyde (MDA), glutathione (GSH), iron and ferroptosis-related protein.
RESULTS: miR-210-3p decreased significantly in mice fed methionine-choline-deficient (MCD)-fed and in those fed a high-fat diet (HFD) + CCL4 diets. Palmitic acid (PA)-stimulated LX2 and primary hepatic stellate cells showed miR-210-3p downregulation, consistent with the microarray results. miR-210-3p overexpression alleviated MASH-related fibrosis by inducing ferroptosis in hepatic stellate cells. Iron-sulfur cluster assembly enzyme (ISCU) was validated as the downstream target of miR-210-3p and its overexpression reversed miR-210-3p-induced ferroptosis. Overall, the ISCU-IRP1-CD71 axis is vital to miR-210-3p-induced ferroptosis.
CONCLUSIONS: miR-210-3p expression is decreased in MASH-related fibrosis and is involved in ferroptosis by targeting ISCU.
METHODS: We examined miR-210-3p expression in patients with MASH, with or without fibrosis using microarray analysis. miR-210-3p expression both in vivo and in vitro was validated using real-time quantitative reverse transcription PCR (RT-qPCR). Target genes and mechanisms were explored using western blotting, dual luciferase assay and immunofluorescence staining. Ferroptosis was assessed based on the levels of malondialdehyde (MDA), glutathione (GSH), iron and ferroptosis-related protein.
RESULTS: miR-210-3p decreased significantly in mice fed methionine-choline-deficient (MCD)-fed and in those fed a high-fat diet (HFD) + CCL4 diets. Palmitic acid (PA)-stimulated LX2 and primary hepatic stellate cells showed miR-210-3p downregulation, consistent with the microarray results. miR-210-3p overexpression alleviated MASH-related fibrosis by inducing ferroptosis in hepatic stellate cells. Iron-sulfur cluster assembly enzyme (ISCU) was validated as the downstream target of miR-210-3p and its overexpression reversed miR-210-3p-induced ferroptosis. Overall, the ISCU-IRP1-CD71 axis is vital to miR-210-3p-induced ferroptosis.
CONCLUSIONS: miR-210-3p expression is decreased in MASH-related fibrosis and is involved in ferroptosis by targeting ISCU.