Anti-Endoglin monoclonal antibody prevents the progression of liver sinusoidal endothelial inflammation and fibrosis in MASH

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10499786" target="_blank" >RIV/00216208:11160/25:10499786 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11150/25:10499786

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=6a58PIe6a9" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=6a58PIe6a9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.lfs.2025.123428" target="_blank" >10.1016/j.lfs.2025.123428</a>

Result language

angličtina

Original language name

Anti-Endoglin monoclonal antibody prevents the progression of liver sinusoidal endothelial inflammation and fibrosis in MASH

Original language description

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 mu g/mL) and treated with TRC105 (300 mu g/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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Life Sciences

ISSN

0024-3205

e-ISSN

1879-0631

Volume of the periodical

364

Issue of the periodical within the volume

March

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

123428

UT code for WoS article

001436435500001

EID of the result in the Scopus database

2-s2.0-85216279589