2. Academic Validation
  3. CDK14 regulates the development and repair of lung

CDK14 regulates the development and repair of lung

  • Cell Death Discov. 2025 Jan 18;11(1):12. doi: 10.1038/s41420-025-02292-4.
Jian-Wei Chen # 1,  Yu-Xiang Wang # 2 3 4,  Rong-Rong Gao # 5,  Lan-Yue Ma 2 3 4,  Jing Zhong 2 3 4,  Jia-Xin Yang 6,  Zhao-Hua Deng 2 3 4,  Yu-Yan Li 2 3 4,  Xiao-Ling Li 2 4,  Ya-Hai Shu 2,  Wen-Jing Guo 2,  Zi-Yuan Zhou 7,  Xiao Yu Tian 8,  Jinjin Ma 9 10,  Yang Liu 11,  Qi Chen 12 13 14 15
Affiliations

Affiliations

  • 1 Institutes of physical science and information technology, Anhui University, Hefei, Anhui, 230601, China.
  • 2 Center for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, 510530, China.
  • 3 University of Chinese Academy of Sciences, Beijing, China.
  • 4 China-New Zealand Belt and Road Joint Laboratory on Biomedicine and Health, Guangdong Provincial Key Laboratory for Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 510530, China.
  • 5 Biomedical 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 Province, Ji'nan, 250117, Shandong, China.
  • 6 The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, 510006, China.
  • 7 National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China.
  • 8 CUHK-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 NT, Hong Kong SAR, 999077, China.
  • 9 The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, 510006, China. [email protected].
  • 10 The Institute of Future Health, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, China. [email protected].
  • 11 The Innovation Centre of Ministry of Education for Development and Diseases, School of Medicine, South China University of Technology, Guangzhou, 510006, China. [email protected].
  • 12 Institutes of physical science and information technology, Anhui University, Hefei, Anhui, 230601, China. [email protected].
  • 13 Center for Cell Lineage Atlas, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, 510530, China. [email protected].
  • 14 China-New Zealand Belt and Road Joint Laboratory on Biomedicine and Health, Guangdong Provincial Key Laboratory for Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 510530, China. [email protected].
  • 15 Biomedical 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 Province, Ji'nan, 250117, Shandong, China. [email protected].
  • # Contributed equally.
PMID: 39827158 DOI: 10.1038/s41420-025-02292-4
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.

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