中文版 | English
Title

Colonic Epithelial PHLPP2 Deficiency Promotes Colonic Epithelial Pyroptosis by Activating the NF-kappa B Signaling Pathway

Author
Corresponding AuthorWu, Ben-hua; Wang, Li-sheng; Bai, Yu; Yao, Jun
Publication Years
2021-08-06
DOI
Source Title
ISSN
1942-0900
EISSN
1942-0994
Volume2021
Abstract
Background. Ulcerative colitis (UC) is a chronic inflammatory disease with increasing prevalence worldwide. Barrier defect in intestinal epithelial cells (IECs) is one of the main pathogeneses in UC. Pyroptosis is a programmed lytic cell death and is triggered by inflammatory caspases, while little is known about its role in UC. Methods. Differentially expressed genes (DEGs) were identified by comparing UC patients with healthy controls from the GEO datasets. The candidate genes involved in pyroptosis were obtained, and the underlying molecular mechanism in the progression of UC was explored in vivo and in vitro. Results. Pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2), a protein phosphatase, was downregulated and involved in regulating inflammation-induced IEC pyroptosis by modulating the NF-kappa B signaling in UC through bioinformatics analysis. Moreover, we demonstrated that PHLPP2 was downregulated in UC patients and UC mice. Besides, we found that PHLPP2 depletion activated the NF-kappa B signaling and increased the expressions of caspase-1 P20, Gasdermin N, IL-18, and IL-1 beta contributing to IEC pyroptosis and inflammation in UC mice. Furthermore, we found that PHLPP2(-/-) mice developed hypersensitivity to dextran sulfate sodium (DSS) treatment toward colitis showing activated NF-kappa B signaling and dramatically induced expressions of caspase-1 P20, Gasdermin N, IL-18, and IL-1 beta. Mechanically, this inflammation-induced downregulation of PHLPP2 was alleviated by an NF-kappa B signaling inhibitor in intestinal organoids of PHLPP2(-/-) mice and fetal colonic cells. Conclusions. PHLPP2 downexpression activated the NF-kappa B signaling and promoted the IEC pyroptosis, leading to UC progression. Therefore, PHLPP2 might be an attractive candidate therapeutic target for UC.
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
First ; Corresponding
Funding Project
Natural Science Foundation of Guangdong Province[2018A0303100024] ; Three Engineering Training Funds in Shenzhen["SYLY201718","SYJY201714","SYLY201801"] ; Technical Research and Development Project of Shenzhen["JCYJ20150403101028164","JCYC20170307100911479","JCYJ20190807145617113"] ; National Natural Science Foundation of China[81800489] ; Shenzhen Health Planning Commission[SZXJ2017030]
WOS Research Area
Cell Biology
WOS Subject
Cell Biology
WOS Accession No
WOS:000820695000003
Publisher
Data Source
Web of Science
Citation statistics
Cited Times [WOS]:7
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/355838
DepartmentShenzhen People's Hospital
Affiliation
1.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Dept Gastroenterol,Clin Med Coll 2,Jinan Univ, Shenzhen 518020, Guangdong, Peoples R China
2.Second Mil Med Univ, Changhai Hosp, Dept Gastroenterol, Shanghai 200082, Peoples R China
3.Gen Hosp Cent Theater Command, Dept Gastroenterol, Wuhan 430000, Hubei, Peoples R China
4.South China Univ, Affiliated Hosp 1, Dept Gastroenterol, Hengyang 421000, Hunan, Peoples R China
First Author AffilicationShenzhen People's Hospital
Corresponding Author AffilicationShenzhen People's Hospital
First Author's First AffilicationShenzhen People's Hospital
Recommended Citation
GB/T 7714
Li, De-feng,Chang, Xin,Zhao, Jiu-long,et al. Colonic Epithelial PHLPP2 Deficiency Promotes Colonic Epithelial Pyroptosis by Activating the NF-kappa B Signaling Pathway[J]. Oxidative Medicine and Cellular Longevity,2021,2021.
APA
Li, De-feng.,Chang, Xin.,Zhao, Jiu-long.,Chen, Xuan-min.,Xu, Zheng-lei.,...&Yao, Jun.(2021).Colonic Epithelial PHLPP2 Deficiency Promotes Colonic Epithelial Pyroptosis by Activating the NF-kappa B Signaling Pathway.Oxidative Medicine and Cellular Longevity,2021.
MLA
Li, De-feng,et al."Colonic Epithelial PHLPP2 Deficiency Promotes Colonic Epithelial Pyroptosis by Activating the NF-kappa B Signaling Pathway".Oxidative Medicine and Cellular Longevity 2021(2021).
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