Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis.

ABSTRACT: Persistent myofibroblast activation distinguishes pathological fibrosis from physiological wound healing, suggesting that therapies selectively inducing myofibroblast apoptosis could prevent progression and potentially reverse established fibrosis in diseases such as scleroderma, a heterogeneous autoimmune disease characterized by multiorgan fibrosis. We demonstrate that fibroblast-to-myofibroblast differentiation driven by matrix stiffness increases the mitochondrial priming (proximity to the apoptotic threshold) of these activated cells. Mitochondria in activated myofibroblasts, but not quiescent fibroblasts, are primed by death signals such as the proapoptotic BH3-only protein BIM, which creates a requirement for tonic expression of the antiapoptotic protein BCL-X_L to sequest

SUBMITTER: Lagares D 

PROVIDER: S-EPMC8520471 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature