Acute contact with profibrotic macrophages mechanically activates fibroblasts via αvβ3 integrin-mediated engagement of Piezo1.

ABSTRACT: Fibrosis-excessive scarring after injury-causes >40% of disease-related deaths worldwide. In this misguided repair process, activated fibroblasts drive the destruction of organ architecture by accumulating and contracting extracellular matrix. The resulting stiff scar tissue, in turn, enhances fibroblast contraction-bearing the question of how this positive feedback loop begins. We show that direct contact with profibrotic but not proinflammatory macrophages triggers acute fibroblast contractions. The contractile response depends on αvβ3 integrin expression on macrophages and Piezo1 expression on fibroblasts. The touch of macrophages elevates fibroblast cytosolic calcium within seconds, followed by translocation of the transcription cofactors nuclear factor of activated T cells 1 and Yes-a

SUBMITTER: Ezzo M 

PROVIDER: S-EPMC11498225 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature