Research Paper Volume 11, Issue 18 pp 7492—7509
PTEN loss regulates alveolar epithelial cell senescence in pulmonary fibrosis depending on Akt activation
- 1 Department of Respiratory Medicine, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing 210008, Jiangsu, People’s Republic of China
- 2 Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, People’s Republic of China
- 3 Department of Respiratory Medicine, KunShan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu 215300, People’s Republic of China
- 4 Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, People’s Republic of China
- 5 Department of Respiratory Medicine, The Affiliated Yixing People Hospital, Jiangsu University, Yixing 214200, Jiangsu, People’s Republic of China
- 6 Jiangsu Key Laboratory of Organ Transplantation, Wuxi People’s Hospital, Nanjing Medical University, Wuxi 214023, Jiangsu, People’s Republic of China
received: February 26, 2019 ; accepted: September 2, 2019 ; published: September 17, 2019 ;https://doi.org/10.18632/aging.102262
How to Cite
Copyright © 2019 Qiu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease with poor prognosis. The mechanisms underlying the role of alveolar epithelial cell (AEC) senescence in IPF remain poorly understood. We aimed to investigate if PTEN/Akt activates AEC senescence to induce pulmonary fibrosis. We investigated the association between PTEN/Akt and cellular senescence in lung tissues from IPF patients. As a result, decreased PTEN and activated Akt pathway were found in AECs in fibrotic lung tissues detected by immunohistochemistry (IHC) and immunofluorescence (IF). Increased expression levels of aging-associated markers (P21WAF1 and SA-β-gal) in AECs treated with bleomycin were found. AEC senescence was accelerated by PTEN knockdown and attenuated by PTEN overexpression. Bleomycin induced AEC senescence was reversed by Akt2 knockdown and the pharmacological inhibitors (LY294002 and MK2206) of the Akt pathway. Reducing Akt activation dramatically improved lung fibrosis in a fibrotic mice model. In addition, a co-immunoprecipitation (co-IP) assay demonstrated that PTEN physically associated with Akt. These indicated that senescent AECs modulated by the PTEN/Akt pathway promote lung fibrosis. In conclusion, our study demonstrated that as a trigger indicator in IPF, the senescence process in AECs should be a potential therapeutic target and that the PTEN/Akt pathway may be a promising candidate for intervention.