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ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 14 - 2024 |
doi: 10.3389/fcimb.2024.1449423
Cdc42 Improve SARS-CoV-2 Spike Protein-Induced Cellular Senescence through Activating of Wnt/β-Catenin signaling pathway
Provisionally accepted
Chunmei Nong
1,2
Zhenzhen Wu
2
Chan Yang
3*
Wei Xu
3
Linyi Luo
4*
Jianping Zhou
5
Lihan Shen
6
Yinghua Chen
6,7*
Yaoqin Yuan
6*
Guodong Hu
1*- 1 Department of Respiratory and Critical Care Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, China
- 2 Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
- 3 Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmacy, Southern Medical University, Guangzhou, China
- 4 The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, China
- 5 Department of Thoracic Surgery，The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, China
- 6 The Tenth Affiliated Hospital of Southern Medical University, Dongguan, China
- 7 Dongguan People’s Hospital Biobank, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, China
COVID-19, caused by SARS-CoV-2, presents a significant public health challenge. SARS-CoV-2 infection drove senescent cells and the senescence-associated phenotypes were reported playing roles in disease progression, which contributes to severe COVID-19 and related sequelae. This study, aimed to investigate the mechanism of the SARS-CoV-2 spike protein regulating cellular senescence. Here, we found the spike protein, SARS-CoV-2 infection related, accelerates cell aging by upregulating Cdc42 expression, which furtherly activated the Wnt/β-Catenin signaling pathway. Conversely, treatment with ML141 in animal models, a Cdc42 inhibitor, reduced cellular senescence and ameliorated lung injury and inflammation. These results suggest that the upregulation of Cdc42 by the SARS-CoV-2 spike protein induces cellular senescence and enhances β-catenin nuclear translocation. This study provides insights into the mechanisms underlying cellular senescence induced by the SARS-CoV-2 spike protein, offering potential strategies to mitigate the inflammatory response and complications associated with COVID-19 in both the acute and long-term phases.
Keywords: SARS-CoV-2, Spike, senescence, Cdc42, β-catenin
Received: 15 Jun 2024; Accepted: 11 Oct 2024.
Copyright: © 2024 Nong, Wu, Yang, Xu, Luo, Zhou, Shen, Chen, Yuan and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chan Yang, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmacy, Southern Medical University, Guangzhou, 510000, China
Linyi Luo, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, China
Yinghua Chen, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, China
Yaoqin Yuan, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, China
Guodong Hu, Department of Respiratory and Critical Care Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, China
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