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FSTL1 promotes alveolar epithelial cell aging and worsens pulmonary fibrosis by affecting SENP1-mediated DeSUMOylation.
Sun, Wei; Yang, Xiaoyu; Chen, Lijuan; Guo, Lu; Huang, Hui; Liu, Xiaoshu; Yang, Yang; Xu, Zuojun.
Affiliation
  • Sun W; Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China.
  • Yang X; Department of Respiratory and Critical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Chen L; Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China.
  • Guo L; Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China.
  • Huang H; Department of Respiratory and Critical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Liu X; Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China.
  • Yang Y; Department of Respiratory and Critical Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China.
  • Xu Z; Department of Respiratory and Critical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cell Biol Int ; 47(10): 1716-1727, 2023 Oct.
Article in En | MEDLINE | ID: mdl-37369969
ABSTRACT
Alveolar epithelial cell (AEC) senescence-induced changes of lung mesenchymal cells are key to starting the progress of pulmonary fibrosis. Follistatin-like 1 (FSTL1) plays a central regulatory role in the complex process of senescence and pulmonary fibrosis by enhancing transforming growth factor-ß1 (TGF-ß1) signal pathway activity. Activation of Smad4 and Ras relies on SUMO-specific peptidase 1 (SENP1)-mediated deSUMOylation during TGF-ß signaling pathway activation. We hypothesized that SENP1-mediated deSUMOylation may be a potential therapeutic target by modulating FSTL1-regulated cellular senescence in pulmonary fibrosis. In verifying this hypothesis, we found that FSTL1 expression was upregulated in the lung tissues of patients with idiopathic pulmonary fibrosis and that SENP1 was overexpressed in senescent AECs. TGF-ß1-induced FSTL1 not only promoted AEC senescence but also upregulated SENP1 expression. Interfering with SENP1 expression inhibited FSTL1-dependent promotion of AEC senescence and improved pulmonary fibrosis in mouse lungs. FSTL1 enhancement of TGF-ß1 signaling pathway activation was dependent on SENP1 in senescent AEC. Our work identifies a novel mechanism by which FSTL1 is involved in AEC senescence. Inhibition of SENP1 in epithelial cells alleviated pulmonary fibrosis by blocking FSTL1-enhanced TGF signaling.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Follistatin-Related Proteins / Idiopathic Pulmonary Fibrosis Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cell Biol Int Year: 2023 Document type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Follistatin-Related Proteins / Idiopathic Pulmonary Fibrosis Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cell Biol Int Year: 2023 Document type: Article Affiliation country: China