Antifibrotic effects of specific targeting of the 5-hydroxytryptamine 2B receptor (5-HT_2BR) in murine models and ex vivo models of scleroderma skin.

ABSTRACT:

Objective

Systemic sclerosis (SSc) is a connective tissue disease with fibrotic remodeling of the skin and various internal organs. SSc is associated with the highest case-specific mortality of all rheumatic autoimmune diseases with limited antifibrotic treatment options. Here, we evaluated the therapeutic effects of the highly selective 5-hydroxytryptamine 2B receptor (5-HT_2BR) inhibitor AM1476.

Methods

The antifibrotic effects of AM1476 were evaluated in the mouse models of bleomycin-induced pulmonary fibrosis in Tsk-1 mice and in mice with sclerodermatous chronic graft-versus-host disease. For further validation, the antifibrotic effects of AM1476 were analyzed in precision cut skin (PCS) slices from patients with SSc.

Results

AM1476 demonstrated high se

SUBMITTER: Trinh-Minh T 

PROVIDER: S-EPMC12311259 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature