Adenosine metabolized from extracellular ATP ameliorates organ injury by triggering A2BR signaling

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dc.authorid0000-0003-3616-1204
dc.contributor.authorKeleştemur, Taha
dc.contributor.authorNémeth, Zoltán H.
dc.contributor.authorPacher, Pal
dc.contributor.authorBeesley, Jennet
dc.contributor.authorRobson, Simon C.
dc.contributor.authorEltzschig, Holger K.
dc.contributor.authorHaskó, György
dc.date.accessioned2023-07-21T07:32:32Z
dc.date.available2023-07-21T07:32:32Z
dc.date.issued2023
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.description.abstractBACKGROUND: Trauma and a subsequent hemorrhagic shock (T/HS) result in insufficient oxygen delivery to tissues and multiple organ failure. Extracellular adenosine, which is a product of the extracellular degradation of adenosine 5' triphosphate (ATP) by the membrane-embedded enzymes CD39 and CD73, is organ protective, as it participates in signaling pathways, which promote cell survival and suppress inflammation through adenosine receptors including the A2BR. The aim of this study was to evaluate the role of CD39 and CD73 delivering adenosine to A2BRs in regulating the host's response to T/HS. METHODS: T/HS shock was induced by blood withdrawal from the femoral artery in wild-type, global knockout (CD39, CD73, A2BR) and conditional knockout (intestinal epithelial cell-specific deficient VillinCre-A2BRfl/fl) mice. At 3 three hours after resuscitation, blood and tissue samples were collected to analyze organ injury. RESULTS: T/HS upregulated the expression of CD39, CD73, and the A2BR in organs. ATP and adenosine levels increased after T/HS in bronchoalveolar lavage fluid. CD39, CD73, and A2BR mimics/agonists alleviated lung and liver injury. Antagonists or the CD39, CD73, and A2BR knockout (KO) exacerbated lung injury, inflammatory cytokines, and chemokines as well as macrophage and neutrophil infiltration and accumulation in the lung. Agonists reduced the levels of the liver enzymes aspartate transferase and alanine transaminase in the blood, whereas antagonist administration or CD39, CD73, and A2BR KO enhanced enzyme levels. In addition, intestinal epithelial cell-specific deficient VillinCre-A2BRfl/fl mice showed increased intestinal injury compared to their wild-type VillinCre controls. CONCLUSION: In conclusion, the CD39-CD73-A2BR axis protects against T/HS-induced multiple organ failure.
dc.identifier.citationKeleştemur, T., Németh, Z. H., Pacher, P., Beesley, J., Robson, S. C., Eltzschig, H. K. ... Haskó, G. (2023). Adenosine metabolized from extracellular ATP ameliorates organ injury by triggering A2BR signaling. Respiratory research, 24(1), 186-186. https://dx.doi.org/10.1186/s12931-023-02486-3
dc.identifier.doi10.1186/s12931-023-02486-3
dc.identifier.endpage186
dc.identifier.issn1465-9921
dc.identifier.issn1465-993X
dc.identifier.issue1
dc.identifier.pmid37438813
dc.identifier.scopus2-s2.0-85164540530
dc.identifier.scopusqualityQ1
dc.identifier.startpage186
dc.identifier.urihttps://dx.doi.org/10.1186/s12931-023-02486-3
dc.identifier.urihttps://hdl.handle.net/20.500.12511/11234
dc.identifier.volume24
dc.identifier.wos001027097600001*
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorKeleştemur, Taha
dc.language.isoen
dc.publisherNLM (Medline)
dc.relation.ispartofRespiratory researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectCD39
dc.subjectCD73
dc.subjectA2BR
dc.subjectAdenosine
dc.subjectAcute Lung Injury
dc.subjectTrauma Hemorrhagic Shock
dc.titleAdenosine metabolized from extracellular ATP ameliorates organ injury by triggering A2BR signaling
dc.typeArticle

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