NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence
Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, and aging-associated interstitial lung disease with a poor prognosis and limited treatment options, while the pathogenesis remains elusive. In this study, we found that the expression of nuclear receptor subfamily 2 group...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-024-02777-3 |
| _version_ | 1797219604539375616 |
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| author | Ruyan Wan Siqi Long Shuaichen Ma Peishuo Yan Zhongzheng Li Kai Xu Hui Lian Wenwen Li Yudi Duan Miaomiao Zhu Lan Wang Guoying Yu |
| author_facet | Ruyan Wan Siqi Long Shuaichen Ma Peishuo Yan Zhongzheng Li Kai Xu Hui Lian Wenwen Li Yudi Duan Miaomiao Zhu Lan Wang Guoying Yu |
| author_sort | Ruyan Wan |
| collection | DOAJ |
| description | Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, and aging-associated interstitial lung disease with a poor prognosis and limited treatment options, while the pathogenesis remains elusive. In this study, we found that the expression of nuclear receptor subfamily 2 group F member 2 (NR2F2), a member of the steroid thyroid hormone superfamily of nuclear receptors, was reduced in both IPF and bleomycin-induced fibrotic lungs, markedly in bleomycin-induced senescent epithelial cells. Inhibition of NR2F2 expression increased the expression of senescence markers such as p21 and p16 in lung epithelial cells, and activated fibroblasts through epithelial-mesenchymal crosstalk, inversely overexpression of NR2F2 alleviated bleomycin-induced epithelial cell senescence and inhibited fibroblast activation. Subsequent mechanistic studies revealed that overexpression of NR2F2 alleviated DNA damage in lung epithelial cells and inhibited cell senescence. Adenovirus-mediated Nr2f2 overexpression attenuated bleomycin-induced lung fibrosis and cell senescence in mice. In summary, these data demonstrate that NR2F2 is involved in lung epithelial cell senescence, and targeting NR2F2 may be a promising therapeutic approach against lung cell senescence and fibrosis. |
| first_indexed | 2024-04-24T12:36:17Z |
| format | Article |
| id | doaj.art-8473b867cb254fbeb89e2617fabf285c |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-24T12:36:17Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-8473b867cb254fbeb89e2617fabf285c2024-04-07T11:27:55ZengBMCRespiratory Research1465-993X2024-04-0125111910.1186/s12931-024-02777-3NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescenceRuyan Wan0Siqi Long1Shuaichen Ma2Peishuo Yan3Zhongzheng Li4Kai Xu5Hui Lian6Wenwen Li7Yudi Duan8Miaomiao Zhu9Lan Wang10Guoying Yu11State Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityState Key Laboratory Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan center for outstanding overseas scientists of pulmonary fibrosis, College of Life Science, Institute of Biomedical Science, Pingyuan Laboratory, Henan Normal UniversityAbstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal, and aging-associated interstitial lung disease with a poor prognosis and limited treatment options, while the pathogenesis remains elusive. In this study, we found that the expression of nuclear receptor subfamily 2 group F member 2 (NR2F2), a member of the steroid thyroid hormone superfamily of nuclear receptors, was reduced in both IPF and bleomycin-induced fibrotic lungs, markedly in bleomycin-induced senescent epithelial cells. Inhibition of NR2F2 expression increased the expression of senescence markers such as p21 and p16 in lung epithelial cells, and activated fibroblasts through epithelial-mesenchymal crosstalk, inversely overexpression of NR2F2 alleviated bleomycin-induced epithelial cell senescence and inhibited fibroblast activation. Subsequent mechanistic studies revealed that overexpression of NR2F2 alleviated DNA damage in lung epithelial cells and inhibited cell senescence. Adenovirus-mediated Nr2f2 overexpression attenuated bleomycin-induced lung fibrosis and cell senescence in mice. In summary, these data demonstrate that NR2F2 is involved in lung epithelial cell senescence, and targeting NR2F2 may be a promising therapeutic approach against lung cell senescence and fibrosis.https://doi.org/10.1186/s12931-024-02777-3NR2F2Cell senescenceDNA damageEpithelial-mesenchymal crosstalkPulmonary fibrosis |
| spellingShingle | Ruyan Wan Siqi Long Shuaichen Ma Peishuo Yan Zhongzheng Li Kai Xu Hui Lian Wenwen Li Yudi Duan Miaomiao Zhu Lan Wang Guoying Yu NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence Respiratory Research NR2F2 Cell senescence DNA damage Epithelial-mesenchymal crosstalk Pulmonary fibrosis |
| title | NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence |
| title_full | NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence |
| title_fullStr | NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence |
| title_full_unstemmed | NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence |
| title_short | NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence |
| title_sort | nr2f2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence |
| topic | NR2F2 Cell senescence DNA damage Epithelial-mesenchymal crosstalk Pulmonary fibrosis |
| url | https://doi.org/10.1186/s12931-024-02777-3 |
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