CDK14 regulates the development and repair of lung
Abstract Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02292-4 |
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| author | Jian-wei Chen Yu-xiang Wang Rong-rong Gao Lan-yue Ma Jing Zhong Jia-xin Yang Zhao-hua Deng Yu-yan Li Xiao-ling Li Ya-hai Shu Wen-jing Guo Zi-yuan Zhou Xiao Yu Tian Jinjin Ma Yang Liu Qi Chen |
| author_facet | Jian-wei Chen Yu-xiang Wang Rong-rong Gao Lan-yue Ma Jing Zhong Jia-xin Yang Zhao-hua Deng Yu-yan Li Xiao-ling Li Ya-hai Shu Wen-jing Guo Zi-yuan Zhou Xiao Yu Tian Jinjin Ma Yang Liu Qi Chen |
| author_sort | Jian-wei Chen |
| collection | DOAJ |
| description | Abstract Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury. Genetic knockout of Cdk14 and the CDK14 covalent inhibitor FMF-04-159-2 resulted in reduction of pulmonary vessel covered area and epithelial cell number, exhibiting increased mortality and more severe lung damage after injury. Mechanistically, Cdk14 ablation inhibited the proliferation of epithelial and vascular endothelial cells, inducing cell cycle arrest at the G2/M phase. Through RNA-seq analysis of both endothelial and epithelial cells, we found that knockdown of Cdk14 controls the expression of signal transducers and activator of transcription 1 (STAT1) as well as associated genes in interferon signaling. Disruption of Cdk14 interferes with IFN-γ induced lung repair in vivo, suggesting potential crosstalk of CDK14 signaling and IFN-γ pathway. Our work highlights the importance of Cdk14 in lung development and regenerative repair through an uncharacterized CDK14- IFN-γ signaling axis. |
| format | Article |
| id | doaj-art-b282a944416848ddbdf19742cb459d71 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-b282a944416848ddbdf19742cb459d712025-01-19T12:10:31ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111410.1038/s41420-025-02292-4CDK14 regulates the development and repair of lungJian-wei Chen0Yu-xiang Wang1Rong-rong Gao2Lan-yue Ma3Jing Zhong4Jia-xin Yang5Zhao-hua Deng6Yu-yan Li7Xiao-ling Li8Ya-hai Shu9Wen-jing Guo10Zi-yuan Zhou11Xiao Yu Tian12Jinjin Ma13Yang Liu14Qi Chen15Institutes of physical science and information technology, Anhui UniversityCenter for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesBiomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences; NHC Key Laboratory of biotechnology drugs (Shandong Academy of Medical Sciences); Key Lab for Rare & Uncommon Diseases of Shandong ProvinceCenter for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyCenter for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeCUHK-GIBH CAS Joint Research Laboratory on Stem Cell and Regenerative Medicine, School of Biomedical Sciences, Heart and Vascular Institute, Faculty of Medicine, The Chinese University of Hong Kong, Shatin NTThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyThe Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of TechnologyInstitutes of physical science and information technology, Anhui UniversityAbstract Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury. Genetic knockout of Cdk14 and the CDK14 covalent inhibitor FMF-04-159-2 resulted in reduction of pulmonary vessel covered area and epithelial cell number, exhibiting increased mortality and more severe lung damage after injury. Mechanistically, Cdk14 ablation inhibited the proliferation of epithelial and vascular endothelial cells, inducing cell cycle arrest at the G2/M phase. Through RNA-seq analysis of both endothelial and epithelial cells, we found that knockdown of Cdk14 controls the expression of signal transducers and activator of transcription 1 (STAT1) as well as associated genes in interferon signaling. Disruption of Cdk14 interferes with IFN-γ induced lung repair in vivo, suggesting potential crosstalk of CDK14 signaling and IFN-γ pathway. Our work highlights the importance of Cdk14 in lung development and regenerative repair through an uncharacterized CDK14- IFN-γ signaling axis.https://doi.org/10.1038/s41420-025-02292-4 |
| spellingShingle | Jian-wei Chen Yu-xiang Wang Rong-rong Gao Lan-yue Ma Jing Zhong Jia-xin Yang Zhao-hua Deng Yu-yan Li Xiao-ling Li Ya-hai Shu Wen-jing Guo Zi-yuan Zhou Xiao Yu Tian Jinjin Ma Yang Liu Qi Chen CDK14 regulates the development and repair of lung Cell Death Discovery |
| title | CDK14 regulates the development and repair of lung |
| title_full | CDK14 regulates the development and repair of lung |
| title_fullStr | CDK14 regulates the development and repair of lung |
| title_full_unstemmed | CDK14 regulates the development and repair of lung |
| title_short | CDK14 regulates the development and repair of lung |
| title_sort | cdk14 regulates the development and repair of lung |
| url | https://doi.org/10.1038/s41420-025-02292-4 |
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