Telomere dysfunction promotes transdifferentiation of human fibroblasts into myofibroblasts.

ABSTRACT: Cells that had undergone telomere dysfunction-induced senescence secrete numerous cytokines and other molecules, collectively called the senescence-associated secretory phenotype (SASP). Although certain SASP factors have been demonstrated to promote cellular senescence in neighboring cells in a paracrine manner, the mechanisms leading to bystander senescence and the functional significance of these effects are currently unclear. Here, we demonstrate that TGF-β1, a component of the SASP, causes telomere dysfunction in normal somatic human fibroblasts in a Smad3/NOX4/ROS-dependent manner. Surprisingly, instead of activating cellular senescence, TGF-β1-induced telomere dysfunction caused fibroblasts to transdifferentiate into α-SMA-expressing myofibroblasts, a mesenchymal and contractile cel

SUBMITTER: Razdan N 

PROVIDER: S-EPMC6260909 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature