兰州大学机构库
Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1
Li, Bin1; Dou, Zhimin1; Zhang, Lei1; Zhu, Lei1; Cao, Yongqiang1; Yu, Q(余勤)2
2021-04-23
Source PublicationFrontiers in Immunology   Impact Factor & Quartile Of Published Year  The Latest Impact Factor & Quartile
ISSN1664-3224
Volume12
page numbers10
AbstractIntestinal barrier dysfunction is an important contributor to morbidity caused by sepsis. This study investigates the molecular mechanism by which Ghrelin affects intestinal dysfunction in rat model of sepsis. A rat model of sepsis was established by cecal ligation and puncture (CLP), revealing that Ghrelin was downregulated when sepsis occurs. Increases in the levels of inflammatory factors tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1 beta), IL-6, gastrin, gamma-H2AX and 8-OHdG was also detected in this model system, as was an overall increase in oxidative stress. Introduction of exogenous Ghrelin inhibited these increases in inflammatory response and oxidative stress, leading to a reduction of overall sepsis-induced intestinal dysfunction. Ghrelin was then shown to activate SIRT1 expression in vitro, while SIRT1 was found to co-express with KLF4, which in turn was predicted to bind to matrix metalloproteinase 2 (MMP2) promoter. Finally, gain- and loss-of-function experiment demonstrated that SIRT1 upregulated the expression of KLF4 to downregulate MMP2. Collectively, Ghrelin inhibits the oxidative stress and intestinal dysfunction to attenuate sepsis by activating SIRT1 and regulating a KLF4/MMP2 regulatory axis.
KeywordsepsisghrelinSIRT1intestinal injuryinflammatory factorKLF4MMP2
PublisherFRONTIERS MEDIA SA
DOI10.3389/fimmu.2021.646775
Indexed BySCOPUS ; SCIE
Language英语
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000648048800001
Original Document TypeArticle
PMID 33968038
Citation statistics
Document Type期刊论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/450202
Collection兰州大学
第一临床医学院
Corresponding AuthorYu, Qin
Affiliation
1.Lanzhou Univ, Dept Crit Med, Hosp 1, Lanzhou, Peoples R China;
2.Lanzhou Univ, Dept Resp, Hosp 1, Sch Clin Med 1, Lanzhou, Peoples R China
First Author AffilicationFirst Clinical School
Corresponding Author AffilicationFirst Clinical School
First Signature AffilicationFirst Clinical School
Recommended Citation
GB/T 7714
Li, Bin,Dou, Zhimin,Zhang, Lei,et al. Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1[J]. Frontiers in Immunology,2021,12.
APA Li, Bin,Dou, Zhimin,Zhang, Lei,Zhu, Lei,Cao, Yongqiang,&Yu, Qin.(2021).Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1.Frontiers in Immunology,12.
MLA Li, Bin,et al."Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1".Frontiers in Immunology 12(2021).
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