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Targeting CCL2-CCR2 signaling pathway alleviates macrophage dysfunction in COPD via PI3K-AKT axis

文献类型：期刊论文

作者Dong, Yue7,8,9,10; Dong, Ying7; Zhu, Chengyue8,9,10; Yang, Lan6; Wang, Hanlin7; Li, Junqing9,10; Zheng, Zixuan5; Zhao, Hanwei5; Xie, Wanji4; Chen, Meiting3
刊名CELL COMMUNICATION AND SIGNALING
出版日期2024-07-17
卷号22期号:1页码:19
关键词Chronic obstructive pulmonary disease C-C motif chemokine ligand 2 C-C chemokine receptor type 2 Bronchial epithelial cells Macrophage
DOI10.1186/s12964-024-01746-z
通讯作者Zang, Yi(yzang@lglab.ac.cn) ; Shi, Jindong(shijindong@fudan.edu.cn)
英文摘要BackgroundChronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide, characterized by persistent respiratory symptoms and airflow limitation. The involvement of C-C motif chemokine ligand 2 (CCL2) in COPD pathogenesis, particularly in macrophage regulation and activation, is poorly understood despite its recognized role in chronic inflammation. Our study aims to elucidate the regulatory role and molecular mechanisms of CCL2 in the pathogenesis of COPD, providing new insights for therapeutic strategies.MethodsThis study focused on the CCL2-CCR2 signaling pathway, exploring its role in COPD pathogenesis using both Ccl2 knockout (KO) mice and pharmacological inhibitors. To dissect the underlying mechanisms, we employed various in vitro and in vivo methods to analyze the secretion patterns and pathogenic effects of CCL2 and its downstream molecular signaling through the CCL2-CCR2 axis.ResultsElevated Ccl2 expression was confirmed in the lungs of COPD mice and was associated with enhanced recruitment and activation of macrophages. Deletion of Ccl2 in knockout mice, as well as treatment with a Ccr2 inhibitor, resulted in protection against CS- and LPS-induced alveolar injury and airway remodeling. Mechanistically, CCL2 was predominantly secreted by bronchial epithelial cells in a process dependent on STAT1 phosphorylation and acted through the CCR2 receptor on macrophages. This interaction activated the PI3K-AKT signaling pathway, which was pivotal for macrophage activation and the secretion of inflammatory cytokines, further influencing the progression of COPD.ConclusionsThe study highlighted the crucial role of CCL2 in mediating inflammatory responses and remodeling in COPD. It enhanced our understanding of COPD's molecular mechanisms, particularly how CCL2's interaction with the CCR2 activates critical signaling pathways. Targeting the CCL2-CCR2 axis emerged as a promising strategy to alleviate COPD pathology.
WOS关键词OBSTRUCTIVE PULMONARY-DISEASE ; PURIFICATION ; RECRUITMENT ; ACTIVATION ; ALIGNMENT ; PROTEIN ; MCP-1
资助项目National Natural Science Foundation of China
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001268909000001
出版者BMC
源URL[http://119.78.100.183/handle/2S10ELR8/312377]  
专题中国科学院上海药物研究所
通讯作者Zang, Yi; Shi, Jindong
作者单位1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Zhongshan Inst Drug Discovery, Zhongshan, Guangdong, Peoples R China
3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
4.Hongqiao Community Healthcare Serv Ctr Minhang Dis, Dept Gen Med, Shanghai, Peoples R China
5.Zhuanqiao Community Healthcare Serv Ctr Minhang Di, Dept Gen Med, Shanghai, Peoples R China
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai, Peoples R China
8.Lingang Lab, 100-19 Banxia Rd, Shanghai 200120, Peoples R China
9.Fudan Univ, Ctr Community Based Hlth Res, Shanghai, Peoples R China
10.Fudan Univ, Shanghai Peoples Hosp 5, Dept Resp & Crit Care Med, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Dong, Yue,Dong, Ying,Zhu, Chengyue,et al. Targeting CCL2-CCR2 signaling pathway alleviates macrophage dysfunction in COPD via PI3K-AKT axis[J]. CELL COMMUNICATION AND SIGNALING,2024,22(1):19.
APA Dong, Yue.,Dong, Ying.,Zhu, Chengyue.,Yang, Lan.,Wang, Hanlin.,...&Shi, Jindong.(2024).Targeting CCL2-CCR2 signaling pathway alleviates macrophage dysfunction in COPD via PI3K-AKT axis.CELL COMMUNICATION AND SIGNALING,22(1),19.
MLA Dong, Yue,et al."Targeting CCL2-CCR2 signaling pathway alleviates macrophage dysfunction in COPD via PI3K-AKT axis".CELL COMMUNICATION AND SIGNALING 22.1(2024):19.

入库方式： OAI收割

来源：上海药物研究所

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