MicroRNA-34b-5p binds enhancer of zeste 2 to inhibit milk fat globule-EGF factor 8 expression, affecting liver fibrosis
J. physiol. biochem
; 78(4): 885-895, nov. 2022.
Article
in English
| IBECS
| ID: ibc-216179
Responsible library:
ES1.1
Localization: ES15.1 - BNCS
ABSTRACT
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. (AU)
Search on Google
Collection:
National databases
/
Spain
Database:
IBECS
Main subject:
MicroRNAs
/
Enhancer of Zeste Homolog 2 Protein
/
Liver Cirrhosis
/
Antigens, Surface
Limits:
Animals
Language:
English
Journal:
J. physiol. biochem
Year:
2022
Document type:
Article
Institution/Affiliation country:
Central South University/People's Republic of China