Elucidation of the pathomechanism of lung fibrosis from the viewpoint of cellular senescence and cytoskeletal organization
Description: In this study, we investigated the roles of epithelial Pten in the pathogenesis of lung fibrosis by using lung epithelial-specific Pten deficient (Pten-KO) mice. Pten-KO mice showed increased cell senescence and enhanced p53 expressions in alveolar epithelial cells (AECs). Pten-KO mice also showed enhanced cellular senescence-associated secretory phenotype in the lungs, and Pten-KO mice at 30 weeks old showed enhanced lung architectural remodeling (increased mean linear intercept of alveoli and alveolar destruction index). Interestingly, AECs of Pten-KO mice showed impaired bipolar spindle formations. These results indicated that epithelial Pten deficiency causes accelerated cellular senescence of AECs through p53 upregulation and the impairment of bipolar spindle formations, and subsequently enhances lung architectural remodeling.
Amount: ¥3,510,000
Funding type: research
Funder scheme: Grant-in-Aid for Challenging Exploratory Research
Start date: 2016-04-01
End date: 2018-03-31
Investigator: Masamitsu Nakazato
Institution: University of Miyazaki
Funded outputs count: 0
Funder award ID: 16K15460
OpenAlex ID: G4950426469