Divergent Regulation of Alveolar Type 2 Cell and Fibroblast Apoptosis by Plasminogen Activator Inhibitor 1 in Lung Fibrosis.

ABSTRACT: Increased apoptosis sensitivity of alveolar type 2 (ATII) cells and increased apoptosis resistance of (myo)fibroblasts, the apoptosis paradox, contributes to the pathogenesis of idiopathic pulmonary fibrosis (IPF). The mechanism underlying the apoptosis paradox in IPF lungs, however, is unclear. Aging is the greatest risk factor for IPF. In this study, we show, for the first time, that ATII cells from old mice are more sensitive, whereas fibroblasts from old mice are more resistant, to apoptotic challenges, compared with the corresponding cells from young mice. The expression of plasminogen activator inhibitor 1 (PAI-1), an important profibrogenic mediator, was significantly increased in both ATII cells and lung fibroblasts from aged mice. In vitro studies using PAI-1 siRNA and active PAI-

SUBMITTER: Jiang C 

PROVIDER: S-EPMC8351125 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature