Investigetion of the pathomechanisims of smoking-related lung disease focusing on tissue stem cell niche
Description: We investigated the role of Pten, a tumor suppressor, in alveolar type 2 (AT2). AT2-specific Pten null mice spontaneously developed age-related emphysema. AT2-specific Pten null mice showed decreased numbers of AT2 and increased numbers of lung mesenchymal cells (LMSc) 8 weeks after tamoxifen treatment. RNA sequencing of isolated AT2 and LMSc identified the perturbation of epithelial-mesenchymal interaction signaling. Deletion of Pten in AT2 increased the number of senescent AT2. Lung epithelial cell-specific Pten deficiency provoked accumulation of dysmorphic and dysfunctional mitochondria with increased reactive oxygen species production. Moreover, lung epithelial cell-specific Pten deletion induced excessive senescence-associated secretory phenotype. Our results highlight that Pten in AT2 has an essential role in controlling age-related emphysema by regulating cellular senescence and epithelial-mesenchymal and mitochondrial homeostasis.
Amount: ¥4,420,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2018-04-01
End date: 2021-03-31
Investigator: Shigehisa Yanagi
Institution: University of Miyazaki
Funded outputs count: 2
Funder award ID: 18K08179
OpenAlex ID: G1139463095