MicroRNA-34b-5p binds enhancer of zeste 2 to inhibit milk fat globule-EGF factor 8 expression, affecting liver fibrosis
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Ma, Jing [1] ; Liu, Qiyao [1] ; Chen, Mengxuan [1] ; He, Bo [1] ; Li, Yi [1] ; Zhang, Min [1] ; Jiang, Yongfang [1]
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[1] Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
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- Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 78, Nº. 4, 2022, págs. 885-895
- Idioma: inglés
- Enlaces
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Resumen
Activated hepatic stellate cells (HSCs) are considered the major drivers in the process of hepatic fibrosis. This study intends to explore the mechanism underlying microRNA (miR)-34b-5p effects over liver fibrosis through the enhancer of zeste 2 (EZH2)/milk fat globule-EGF factor 8 (MFGE8) axis in HSCs. A liver fibrosis model was generated by carbon tetrachloride (CCl4) in C57BL/6 J mice and subjected to histological examinations and detection of HSC activation and miR-34b-5p/EZH2/MFGE8 expression. Primary HSCs were treated with transforming growth factor (TGF)-β and tested for proliferation, activation, and expression of fibrosis-related factors. A dual luciferase reporter assay was performed for confirming the targeted relationship between miR-34b-5p and EZH2. Chromatin immunoprecipitation was used to measure EZH2 enrichment in the MFGE8 promoter region. We found that miR-34b-5p was lowly expressed in the CCl4-induced mouse model. Overexpression of miR-34b-5p suppressed both TGF-β-induced HSC proliferation and the expression of fibrosis-related factors and HSC activation markers. A dual luciferase assay showed a binding relationship between miR-34b-5p and EZH2. Overexpression of miR-34b-5p reduced TGF-β-induced HSC activation by inhibiting EZH2 to promote MFGE8 expression. Overexpression of miR-34b-5p inhibited liver fibrosis in vivo through the EZH2/MFGE8 axis. Conclusively, overexpressing miR-34b-5p reduced TGF-β-induced HSC activation by inhibiting EZH2 and thereby promoting MFGE8 expression, and inhibited liver fibrosis in vivo through the EZH2/MFGE8 axis.
