2. Academic Validation
  3. CircCDC42-encoded CDC42-165aa regulates macrophage pyroptosis in Klebsiella pneumoniae infection through Pyrin inflammasome activation

CircCDC42-encoded CDC42-165aa regulates macrophage pyroptosis in Klebsiella pneumoniae infection through Pyrin inflammasome activation

  • Nat Commun. 2024 Jul 8;15(1):5730. doi: 10.1038/s41467-024-50154-x.
Nana Xu # 1 2,  Jiebang Jiang # 1,  Fei Jiang 1 3,  Guokai Dong 1 2,  Li Meng 1 2,  Meng Wang 1 2,  Jing Chen 1,  Cong Li 4,  Yongping Shi 5,  Sisi He 6,  Rongpeng Li 7
Affiliations

Affiliations

  • 1 Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, China.
  • 2 Laboratory of Morphology, Xuzhou Medical University, Xuzhou, China.
  • 3 Department of Laboratory Medicine, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 4 Xuzhou Key Laboratory of Emergency Medicine, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 5 Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, China. shiyongp@sina.com.
  • 6 Department of Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China. sisihe1219@163.com.
  • 7 Jiangsu Province Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, School of Life Sciences, Jiangsu Normal University, Xuzhou, China. lirongpeng@jsnu.edu.cn.
  • # Contributed equally.
PMID: 38977695 DOI: 10.1038/s41467-024-50154-x
Abstract

The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, Cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)-165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage Pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP Infection by inhibiting Pyrin inflammasome-mediated Pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic Bacterial infection in clinical practice.

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