Serpine 1 induces alveolar type II cell senescence through activating p53-p21-Rb pathway in fibrotic lung disease.

ABSTRACT: Senescence of alveolar type 2 (ATII) cells, progenitors of the alveolar epithelium, is implicated in the pathogeneses of idiopathic pulmonary fibrosis (IPF), an aging-related progressive fatal lung disorder with unknown etiology. The mechanism underlying ATII cell senescence in fibrotic lung diseases, however, remains poorly understood. In this study, we report that ATII cells in IPF lungs express higher levels of serpine 1, also known as plasminogen activator inhibitor 1 (PAI-1), and cell senescence markers p21 and p16, compared to ATII cells in control lungs. Silencing PAI-1 or inhibition of PAI-1 activity in cultured rat ATII (L2) cells leads to decreases in p53 serine 18 phosphorylation (p53^S18P ), p53 and p21 protein expressions; an increase in retinoblastoma protein phosph

SUBMITTER: Jiang C 

PROVIDER: S-EPMC5595683 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature