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CDK14 regulates the development and repair of lung

Jian-Wei Chen1, Yu-Xiang Wang2,3,4, Rong-Rong Gao5

  • 1Institutes of physical science and information technology, Anhui University, Hefei, Anhui, 230601, China.

Cell Death Discovery
|January 18, 2025
PubMed

Insights

Cyclin-dependent kinases (CDK) 14 is crucial for lung development and repair. Genetic knockout of CDK14 impairs lung regeneration and increases mortality by affecting cell proliferation and interferon signaling.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Pulmonary Medicine

Background:

  • Cyclin-dependent kinases (CDK) 14 regulates cell cycle and Wnt signaling, impacting tumor growth.
  • The role of CDK14 in organ development and regeneration remains largely unexplored.

Purpose of the Study:

  • To investigate the function of CDK14 in mouse lung development and repair following injury.
  • To elucidate the molecular mechanisms underlying CDK14's role in lung regeneration.

Main Methods:

  • Genetic ablation of Cdk14 in mice.
  • Induction of lung injury using bleomycin or lipopolysaccharide.
  • Assessment of lung vascular and epithelial compartments.
  • RNA-sequencing (RNA-seq) analysis of endothelial and epithelial cells.
  • Pharmacological inhibition of CDK14 using FMF-04-159-2.

Main Results:

  • Genetic knockout of Cdk14 impaired lung development and repair, leading to reduced pulmonary vessel coverage and epithelial cell numbers.
  • Cdk14 deficiency caused cell cycle arrest at G2/M phase in pulmonary vascular and epithelial cells.
  • RNA-seq revealed that Cdk14 regulates Signal Transducer and Activator of Transcription 1 (STAT1) and interferon signaling pathways.
  • Disruption of Cdk14 interfered with interferon-gamma (IFN-γ)-induced lung repair in vivo.

Conclusions:

  • CDK14 plays a critical role in lung development and regenerative repair.
  • A novel CDK14-IFN-γ signaling axis is identified, highlighting its importance in lung injury response.
  • Targeting CDK14 may offer therapeutic potential for lung diseases involving impaired regeneration.

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