
lveolar epithelial cell (AEC) senescence is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Mitochondrial dysfunction including release of mitochondrial DNA is a feature of senescence, which led us to investigate the role of the DNA-sensing GMP-AMP synthase in IPF, with a focus on AEC senescence.cGAS expression in fibrotic tissue from lungs of IPF patients was detected within cells immunoreactive for epithelial cell adhesion molecule and p21, epithelial and senescence markers respectively. 521 diminished IPF-AEC senescence in culture and attenuated induction of Ctrl-AEC senescence following etoposide-induced DNA damage. Furthermore, ectopic mtDNA augmented cGAS-dependent senescence of Ctrl-AECs, whereas DNAse I treatment diminished IPF-AEC senescence.
Like
Save
Share