Targeting PIM1 by Bruceine D attenuates skin fibrosis via myofibroblast ferroptosis.

ABSTRACT: Skin pan-fibrosis diseases-such as hypertrophic scar (HS), keloid scar (KS), and systemic sclerosis (SSc)-pose significant threats to patients' health and quality of life. In this study, the authors conducted both in vivo and in vitro experiments and discovered that the serine/threonine kinase PIM1 is upregulated in the myofibroblasts of human HS, KS, and SSc tissues, as well as in various animal models of skin fibrosis. Overexpression of PIM1 enhanced the profibrotic phenotypes of human hypertrophic scar fibroblasts (HSFs), which serve as key effector cells in the pathogenesis of skin pan-fibrosis diseases. Through high-throughput screening and subsequent laboratory assays, we identified the small molecule Bruceine D (BD) as a direct binder of PIM1. BD promoted ferroptosis in HSFs by sele

SUBMITTER: Wang J 

PROVIDER: S-EPMC11993190 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature