PAK1 Promotes Inflammation Induced by Sepsis through the Snail/CXCL2 Signaling Pathway

doi:10.1021/acsinfecdis.4c00052

科研成果详情

题名	PAK1 Promotes Inflammation Induced by Sepsis through the Snail/CXCL2 Signaling Pathway
作者	Chen, Miaomiao 1; Pan, Liuhua 1; Chen, Deyuan 1; Wu, Yueming 1; Ye, Jianping1; Li, Ke 1; Zhang, Ning 2; Xu, Junlong 1
发表日期	2024-03-19
发表期刊	ACS INFECTIOUS DISEASES 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	sepsis PAK1 CXCL2 snail inflammation response
其他关键词	IL-38
摘要	Sepsis is a severe syndrome characterized by organ dysfunction, resulting from a systemic imbalance in response to infection. PAK1 plays a critical role in various diseases. The present study aimed to explore and delineate the mechanism of PAK1 in inflammation induced by sepsis. Bioinformatics analysis was performed to assess PAK1, snail, and CXCL2 expression in the whole blood of septic patients and the pathways enriched with PAK1. To simulate the sepsis model, THP-1 cells were stimulated with lipopolysaccharide. Gene expression was evaluated using qRT-PCR, while cell viability was assessed using CCK-8 assay. Cell apoptosis was tested with flow cytometry. Expression of inflammatory factors in cells following different treatments was analyzed using the enzyme linked immunosorbent assay (ELISA). Dual-luciferase and chromatin immunoprecipitation assays were conducted to verify the binding relationship between PAK1 and the snail. Mouse models of cecal ligation and puncture were established, and hematoxylin and eosin staining and ELISA were employed to detect the infiltration levels of inflammatory cells and the expression of related protective factors in lung, liver, and kidney tissues. The results demonstrated upregulation of PAK1, snail, and CXCL2 in the whole blood of septic patients, with PAK1 being enriched in the chemokine-related pathway. Knockdown of PAK1 significantly promoted the apoptosis of LPS-stimulated THP-1 cells and inhibited the expression of inflammatory factors. PAK1 upregulated the expression of the snail, which in turn promoted the expression of CXCL2. Thus, PAK1 mediated the sepsis-induced inflammatory response through the snail/CXCL2 pathway. In conclusion, PAK1 played a role in promoting inflammation induced by sepsis through the snail/CXCL2 axis, thereby providing a potential therapeutic target for the management of sepsis.
资助项目	Zhejiang Province Basic Public Welfare Research Program [LGF20H150008]
出版者	AMER CHEMICAL SOC
ISSN	2373-8227
卷号	10 期号:4 页码:1370-1378
DOI	10.1021/acsinfecdis.4c00052
页数	9
WOS类目	Chemistry, Medicinal ; Infectious Diseases
WOS研究方向	Pharmacology & Pharmacy ; Infectious Diseases
WOS记录号	WOS:001187673700001
收录类别	SCIE ; PUBMED ; SCOPUS
在线发表日期	2024-03
URL	查看原文
PubMed ID	38503263
SCOPUSEID	2-s2.0-85188244959
通讯作者地址	[Zhang, Ning]Department of Emergency Medicine,The Six Affiliated Hospital of Wenzhou Medical University,Lishui,323000,China ; [Xu, Junlong]Department of Critical Care Medicine,The Six Affiliated Hospital of Wenzhou Medical University,Lishui,323000,China
Scopus学科分类	Infectious Diseases
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/209985
专题	温州医科大学第一临床医学院（信息与工程学院）、附属第一医院_急诊医学
通讯作者	Zhang, Ning; Xu, Junlong
作者单位	1.Department of Critical Care Medicine,The Six Affiliated Hospital of Wenzhou Medical University,Lishui,323000,China; 2.Department of Emergency Medicine,The Six Affiliated Hospital of Wenzhou Medical University,Lishui,323000,China
第一作者单位	温州医科大学
通讯作者单位	第一临床医学院（信息与工程学院）、附属第一医院_急诊医学; 温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Chen, Miaomiao,Pan, Liuhua,Chen, Deyuan,et al. PAK1 Promotes Inflammation Induced by Sepsis through the Snail/CXCL2 Signaling Pathway[J]. ACS INFECTIOUS DISEASES,2024,10(4):1370-1378.
APA	Chen, Miaomiao., Pan, Liuhua., Chen, Deyuan., Wu, Yueming., Ye, Jianping., ... & Xu, Junlong. (2024). PAK1 Promotes Inflammation Induced by Sepsis through the Snail/CXCL2 Signaling Pathway. ACS INFECTIOUS DISEASES, 10(4), 1370-1378.
MLA	Chen, Miaomiao,et al."PAK1 Promotes Inflammation Induced by Sepsis through the Snail/CXCL2 Signaling Pathway".ACS INFECTIOUS DISEASES 10.4(2024):1370-1378.