Translational engagement of lysophosphatidic acid receptor 1 in skin fibrosis: from dermal fibroblasts of patients with scleroderma to tight skin 1 mouse.

ABSTRACT:

Background and purpose

Genetic deletion and pharmacological studies suggest a role for lysophosphatidic acid (LPA₁ ) receptor in fibrosis. We investigated the therapeutic potential in systemic sclerosis (SSc) of a new orally active selective LPA₁ receptor antagonist using dermal fibroblasts from patients and an animal model of skin fibrosis.

Experimental approach

Dermal fibroblast and skin biopsies from systemic sclerosis patients were used. Myofibroblast differentiation, gene expression and cytokine secretion were measured following LPA and/or SAR100842 treatment. Pharmacolgical effect of SAR100842 was assessed in the tight skin 1 (Tsk1) mouse model.

Key results

SAR100842 is equipotent against various LPA isoforms. Dermal fibroblasts and skin bi

SUBMITTER: Ledein L 

PROVIDER: S-EPMC7443477 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature