Anti-Endoglin monoclonal antibody prevents the progression of liver sinusoidal endothelial inflammation and fibrosis in MASH
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
39889923
DOI
10.1016/j.lfs.2025.123428
PII: S0024-3205(25)00061-X
Knihovny.cz E-resources
- Keywords
- Anti-endoglin antibody, Endoglin, Fibrosis, Liver alteration, Liver sinusoidal endothelial inflammation,
- MeSH
- Diet, High-Fat adverse effects MeSH
- Endothelial Cells drug effects pathology metabolism MeSH
- Liver Cirrhosis * prevention & control pathology MeSH
- Liver pathology drug effects metabolism MeSH
- Rats MeSH
- Humans MeSH
- Antibodies, Monoclonal * pharmacology therapeutic use MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Non-alcoholic Fatty Liver Disease MeSH
- Disease Progression MeSH
- Inflammation * pathology prevention & control drug therapy MeSH
- Fatty Liver * pathology drug therapy MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antibodies, Monoclonal * MeSH
Liver sinusoidal endothelial inflammation/dysfunction and fibrosis are a crucial part of Metabolic Dysfunction Associated Steatohepatitis (MASH) development. TRC105 and M1043 are anti-endoglin (ENG) monoclonal antibodies that bind ENG. In this study, we hypothesized that treatment with anti-ENG antibodies would prevent the progression of LSECs inflammation and fibrosis in vivo and in vitro. MASH was induced in male C57BL/6 mice fed a choline-deficient L-amino acid-defined high-fat diet (CDAA-HFD) for 4 or 8 weeks. In the rescue study, mice were divided into three groups: a control group (chow diet), a MASH group (CDAA-HFD + IgG), and a rescue group (CDAA-HFD + M1043). Later, two groups received rat IgG1 (10 mg/kg) and M1043 (10 mg/kg). In in vitro experiments, inflammation was induced in human LSECs by ox-LDL (50 μg/mL) and treated with TRC105 (300 μg/mL). Liver sinusoidal endothelial inflammation/dysfunction in MASH animals was characterized by endothelial overexpression of ENG, VCAM-1, and ICAM-1 and reduced VE-cadherin and p-eNOS/eNOS expression. M1043 treatment prevented the overexpression of ENG, VCAM-1, and ICAM-1, the progression of liver fibrosis, and the increase of liver-to-body weight ratio. In vitro experiments with TRC105 confirmed the prevention of LSECs inflammation development by reduced ENG and VCAM-1 expression, as well as decreased THP-1 monocytic cell adhesion in ox-LDL activated LSECs. In conclusion, we demonstrate that anti-ENG antibody treatment can prevent LSECs inflammation and fibrosis progression in a MASH animal model and LSECs inflammation in vitro. Thus, we propose directly targeted ENG may represent a promising pharmacological approach for addressing LSECs inflammation and liver fibrosis.
References provided by Crossref.org
