| Title: | EDIL3 Deficiency Attenuates Liver Fibrosis Through Inhibiting Hepatic Stellate Cells Activation via the Integrin αvβ3-ERK1/2-RUNX2 Axis in MASH Mice |
| Journal: | The FASEB Journal |
| Published: | 23 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40699913/ |
| DOI: | https://doi.org/10.1096/fj.202403088r |
Publication 17016
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Abstract
Metabolic Dysfunction-Associated Steatohepatitis (MASH) emerges as an advanced stage of Metabolic Dysfunction-Associated Steatotic Liver Disease, marked by significant liver damage characterized by fat accumulation, inflammation, hepatocyte injury, and progressive fibrosis. Epidermal Growth Factor-like repeat and Discoidin I-like domain-containing protein 3 (EDIL3), a protein containing epidermal growth factor-like repeats and discoidin I-like domains, interacts with membrane integrins to modulate inflammation, fibrosis, and vascular remodeling. However, the potential role of EDIL3 in the progression of liver fibrosis in MASH remains unclear. Our study unveiled a significant correlation between plasma EDIL3 levels and liver fibrosis severity in a UK Biobank population. In choline-deficient, L-amino acid-defined high-fat diet-induced MASH mouse models, EDIL3 liver expression was markedly upregulated, whereas EDIL3 deficiency mitigated liver damage, lipid accumulation, and fibrosis. Transcriptomic analysis indicated that EDIL3 deficiency substantially impacts extracellular matrix-related processes and inhibits Hepatic Stellate Cells (HSCs) activation in MASH. Mechanistically, EDIL3 binds to integrin αvβ3, activating HSCs via the ERK1/2-RUNX2 pathway. In summary, our findings demonstrate that EDIL3 regulates HSC activation through the integrin αvβ3-ERK1/2-RUNX2 axis, influencing liver fibrosis in MASH, thus offering a potential therapeutic avenue for MASH and fibrotic liver diseases.</p>
14 Keywords
- Animals
- Core Binding Factor Alpha 1 Subunit
- Diet, High-Fat
- Fatty Liver
- Hepatic Stellate Cells
- Humans
- Integrin alphaVbeta3
- Liver Cirrhosis
- MAP Kinase Signaling System
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Non-alcoholic Fatty Liver Disease
6 Authors
- Cheng Wei
- Dongwei Lu
- Jianfang Liu
- Juan-Juan Qin
- Menglong Wang
- Fang Lei
1 Application
| Application ID | Title |
|---|---|
| 96962 | Identifying the association factors and causal determinants in aging and aging-related diseases. |
Enabling scientific discoveries that improve human health