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YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis.
- Source :
-
Experimental & molecular medicine [Exp Mol Med] 2024 Jul; Vol. 56 (7), pp. 1643-1654. Date of Electronic Publication: 2024 Jul 01. - Publication Year :
- 2024
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Abstract
- The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Humans
Adaptor Proteins, Signal Transducing metabolism
Adaptor Proteins, Signal Transducing genetics
Male
Bleomycin
Transcription Factors metabolism
Transcription Factors genetics
Idiopathic Pulmonary Fibrosis metabolism
Idiopathic Pulmonary Fibrosis pathology
Idiopathic Pulmonary Fibrosis etiology
Disease Models, Animal
Cell Line
YAP-Signaling Proteins metabolism
Alveolar Epithelial Cells metabolism
Cellular Senescence
Pulmonary Fibrosis metabolism
Pulmonary Fibrosis pathology
Pulmonary Fibrosis etiology
Subjects
Details
- Language :
- English
- ISSN :
- 2092-6413
- Volume :
- 56
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Experimental & molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38945958
- Full Text :
- https://doi.org/10.1038/s12276-024-01277-0