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

Nana Xu, Jiebang Jiang, Fei Jiang, Guokai Dong, Li Meng, Meng Wang, Jing Chen, Cong Li, Yongping Shi (), Sisi He () and Rongpeng Li ()
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Nana Xu: Jiangsu Normal University
Jiebang Jiang: Jiangsu Normal University
Fei Jiang: Jiangsu Normal University
Guokai Dong: Jiangsu Normal University
Li Meng: Jiangsu Normal University
Meng Wang: Jiangsu Normal University
Jing Chen: Jiangsu Normal University
Cong Li: the Affiliated Hospital of Xuzhou Medical University
Yongping Shi: Jiangsu Normal University
Sisi He: The Second Affiliated Hospital of Zunyi Medical University
Rongpeng Li: Jiangsu Normal University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50154-x

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