A PINCH-1-Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation.

ABSTRACT: Mechano-environment plays multiple critical roles in the control of mesenchymal stem cell (MSC) fate decision, but the underlying signaling mechanisms remain undefined. We report here a signaling axis consisting of PINCH-1, SMAD specific E3 ubiquitin protein ligase 1 (Smurf1), and bone morphogenetic protein type 2 receptor (BMPR2) that links mechano-environment to MSC fate decision. PINCH-1 interacts with Smurf1, which inhibits the latter from interacting with BMPR2 and consequently suppresses BMPR2 degradation, resulting in augmented BMP signaling and MSC osteogenic differentiation (OD). Extracellular matrix (ECM) stiffening increases PINCH-1 level and consequently activates this signaling axis. Depletion of PINCH-1 blocks stiff ECM-induced BMP signaling and OD, whereas overexpression of

SUBMITTER: Guo L 

PROVIDER: S-EPMC6829670 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature