摘要
Abstract
Objective To investigate expression changes and regulatory roles of adhesion G protein-coupled receptor F1(ADGRF1/GPR110)in metabolic dysfunction-associated steatohepatitis(MASH)-related hepatic fibrosis.Methods Human MASH liver tissues were collected for GPR110 detection via real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)and immunohistochemistry.Eight-week-old male C57BL/6 mice were randomly divided into four groups:control+AAV-GFP group,control+AAV-GPR110 group,MASH+AAV-GFP group,and MASH+AAV-GPR110 group.MASH was induced by high-fat with high-sucrose diet and low-dose CCl4 intraperitoneal injections,with AAV-GPR110/AAV-GFP delivered via tail vein.Liver tissues were harvested at designated intervals(4 w,8 w,and 12 w).Western blotting measured GPR110 expression;hematoxylin-eosin and oil red O staining assessed histology and lipid content;F4/80 and α-smooth muscle actin(α-SMA)immunofluorescence staining evaluated inflammation and fibrosis;qRT-PCR quantified hepatic expression of lipid metabolism,inflammatory,and fibrotic genes.Results GPR110 expression was significantly reduced in livers of MASH patients compared with controls(P＜0.05).MASH+AAV-GPR110 mice exhibited lower weight,liver index,and serum lipids compared with MASH+AAV-GFP(P＜0.05).Lipid synthesis-related gene(SCD-1),lipid uptake-related gene(CD36),gluconeogenesis-related genes(PEPCK and G-6-Pase),and inflammation-related genes(TNF-α,NF-κB,and iNOS)in liver were downregulated in MASH+AAV-GPR110(P＜0.05).Hepatic F4/80+and α-SMA+areas decreased in MASH+AAV-GPR110(P＜0.05).Conclusion GPR110 overexpression ameliorates hepatic lipid accumulation,reduces inflammation,and delays fibrosis in MASH.关键词
黏附G蛋白偶联受体F1/代谢功能障碍相关脂肪性肝炎/脂质代谢/肝纤维化Key words
adhesion G protein-coupled receptor F1/metabolic dysfunction-associated steatohepatitis/lipid metabolism/hepatic fibrosis分类
临床医学
