Expression changes and functional role of GPR110 in metabolic dysfunction-associated steatohepatitis
ObjectiveTo investigate expression changes and regulatory roles of adhesion G protein-coupled receptor F1 (ADGRF1/GPR110) in metabolic dysfunction-associated steatohepatitis (MASH)-related hepatic fibrosis. MethodsHuman MASH liver tissues were collected for GPR110 detection via real-time quantitativ...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Shanghai Chinese Clinical Medicine Press Co., Ltd.
2025-06-01
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| Series: | Zhongguo Linchuang Yixue |
| Subjects: | |
| Online Access: | https://www.c-jcm.com/article/doi/10.12025/j.issn.1008-6358.2025.20250388 |
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| Summary: | ObjectiveTo investigate expression changes and regulatory roles of adhesion G protein-coupled receptor F1 (ADGRF1/GPR110) in metabolic dysfunction-associated steatohepatitis (MASH)-related hepatic fibrosis. MethodsHuman 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. ResultsGPR110 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). ConclusionGPR110 overexpression ameliorates hepatic lipid accumulation, reduces inflammation, and delays fibrosis in MASH. |
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| ISSN: | 1008-6358 |