A new role for Bcl-XL in fibrosis

In a paper published in Science Translational Medicine, researchers from Harvard Medical School and colleagues suggest that inhibiting the anti-apoptotic protein Bcl-XL could treat fibrosis and describe a cell-based assay to stratify scleroderma patients into Bcl-XL inhibitor responders and non-responders.

Normal physiological conditions such as increased matrix stiffness during wound healing activate differentiation of fibroblasts into myofibroblasts. The authors showed this differentiation process promoted a phenomenon dubbed "mitochondrial priming" in which cells are primed for mitochondrial depolarization and apoptosis via mitochondrial accumulation of pro-apoptotic proteins. However, during fibrotic disease, myofibroblasts fail to undergo apoptosis despite priming...