Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between β-Catenin and NF-κB
Sepsis is characterized by multiple-organ dysfunction caused by the dysregulated host response to infection. Until now, however, the role of the Wnt signaling has not been fully characterized in multiple organs during sepsis. This study assessed the suppressive effect of a Wnt signaling inhibitor, W...
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Veröffentlicht in: | International journal of molecular sciences 2021-06, Vol.22 (12), p.6249 |
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description | Sepsis is characterized by multiple-organ dysfunction caused by the dysregulated host response to infection. Until now, however, the role of the Wnt signaling has not been fully characterized in multiple organs during sepsis. This study assessed the suppressive effect of a Wnt signaling inhibitor, Wnt-C59, in the kidney, lung, and liver of lipopolysaccharide-induced endotoxemic mice, serving as an animal model of sepsis. We found that Wnt-C59 elevated the survival rate of these mice and decreased their plasma levels of proinflammatory cytokines and organ-damage biomarkers, such as BUN, ALT, and AST. The Wnt/β-catenin and NF-κB pathways were stimulated and proinflammatory cytokines were upregulated in the kidney, lung, and liver of endotoxemic mice. Wnt-C59, as a Wnt signaling inhibitor, inhibited the Wnt/β-catenin pathway, and its interaction with the NF-κB pathway, which resulted in the inhibition of NF-κB activity and proinflammatory cytokine expression. In multiple organs of endotoxemic mice, Wnt-C59 significantly reduced the β-catenin level and interaction with NF-κB. Our findings suggest that the anti-endotoxemic effect of Wnt-C59 is mediated via reducing the interaction between β-catenin and NF-κB, consequently suppressing the associated cytokine upregulation in multiple organs. Thus, Wnt-C59 may be useful for the suppression of the multiple-organ dysfunction during sepsis. |
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Until now, however, the role of the Wnt signaling has not been fully characterized in multiple organs during sepsis. This study assessed the suppressive effect of a Wnt signaling inhibitor, Wnt-C59, in the kidney, lung, and liver of lipopolysaccharide-induced endotoxemic mice, serving as an animal model of sepsis. We found that Wnt-C59 elevated the survival rate of these mice and decreased their plasma levels of proinflammatory cytokines and organ-damage biomarkers, such as BUN, ALT, and AST. The Wnt/β-catenin and NF-κB pathways were stimulated and proinflammatory cytokines were upregulated in the kidney, lung, and liver of endotoxemic mice. Wnt-C59, as a Wnt signaling inhibitor, inhibited the Wnt/β-catenin pathway, and its interaction with the NF-κB pathway, which resulted in the inhibition of NF-κB activity and proinflammatory cytokine expression. In multiple organs of endotoxemic mice, Wnt-C59 significantly reduced the β-catenin level and interaction with NF-κB. Our findings suggest that the anti-endotoxemic effect of Wnt-C59 is mediated via reducing the interaction between β-catenin and NF-κB, consequently suppressing the associated cytokine upregulation in multiple organs. Thus, Wnt-C59 may be useful for the suppression of the multiple-organ dysfunction during sepsis.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22126249</identifier><identifier>PMID: 34200709</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Animal models ; Bacteria ; Biomarkers ; Cancer ; Cytokine storm ; Cytokines ; Genotype & phenotype ; Gram-negative bacteria ; Inflammation ; Inhibitors ; Kidneys ; Lipopolysaccharides ; Liver ; Localization ; Lungs ; Microscopy ; NF-κB protein ; Organs ; Plasma ; Plasma levels ; Proteins ; Sepsis ; Signal transduction ; Transcription factors ; Wnt protein ; β-Catenin</subject><ispartof>International journal of molecular sciences, 2021-06, Vol.22 (12), p.6249</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-e884a00e9a81feab618fe9cc9e6f760a1b9cc8d75de79419c49dcfa14eff49e33</citedby><cites>FETCH-LOGICAL-c389t-e884a00e9a81feab618fe9cc9e6f760a1b9cc8d75de79419c49dcfa14eff49e33</cites><orcidid>0000-0002-9823-4555 ; 0000-0002-8937-3182</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230366/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230366/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Jang, Jaewoong</creatorcontrib><creatorcontrib>Song, Jaewon</creatorcontrib><creatorcontrib>Sim, Inae</creatorcontrib><creatorcontrib>Kwon, Young V.</creatorcontrib><creatorcontrib>Yoon, Yoosik</creatorcontrib><title>Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between β-Catenin and NF-κB</title><title>International journal of molecular sciences</title><description>Sepsis is characterized by multiple-organ dysfunction caused by the dysregulated host response to infection. Until now, however, the role of the Wnt signaling has not been fully characterized in multiple organs during sepsis. This study assessed the suppressive effect of a Wnt signaling inhibitor, Wnt-C59, in the kidney, lung, and liver of lipopolysaccharide-induced endotoxemic mice, serving as an animal model of sepsis. We found that Wnt-C59 elevated the survival rate of these mice and decreased their plasma levels of proinflammatory cytokines and organ-damage biomarkers, such as BUN, ALT, and AST. The Wnt/β-catenin and NF-κB pathways were stimulated and proinflammatory cytokines were upregulated in the kidney, lung, and liver of endotoxemic mice. Wnt-C59, as a Wnt signaling inhibitor, inhibited the Wnt/β-catenin pathway, and its interaction with the NF-κB pathway, which resulted in the inhibition of NF-κB activity and proinflammatory cytokine expression. In multiple organs of endotoxemic mice, Wnt-C59 significantly reduced the β-catenin level and interaction with NF-κB. Our findings suggest that the anti-endotoxemic effect of Wnt-C59 is mediated via reducing the interaction between β-catenin and NF-κB, consequently suppressing the associated cytokine upregulation in multiple organs. Thus, Wnt-C59 may be useful for the suppression of the multiple-organ dysfunction during sepsis.</description><subject>Animal models</subject><subject>Bacteria</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cytokine storm</subject><subject>Cytokines</subject><subject>Genotype & phenotype</subject><subject>Gram-negative bacteria</subject><subject>Inflammation</subject><subject>Inhibitors</subject><subject>Kidneys</subject><subject>Lipopolysaccharides</subject><subject>Liver</subject><subject>Localization</subject><subject>Lungs</subject><subject>Microscopy</subject><subject>NF-κB protein</subject><subject>Organs</subject><subject>Plasma</subject><subject>Plasma levels</subject><subject>Proteins</subject><subject>Sepsis</subject><subject>Signal transduction</subject><subject>Transcription factors</subject><subject>Wnt protein</subject><subject>β-Catenin</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkstu1DAUhi0EoqWw4wEssWFBwLck9gYJohZGmlKJUrGMHOck4yGxU9spzGuxZMcL9JnItBUqrM7t0_8f6RyEnlPymnNF3tjtGBmjrGBCPUCHVDCWEVKUD-_lB-hJjFtCGGe5eowOuGCElEQdot9fXcrObe_0YF2PV25jG5t8wPt-lSt8Pk9TgBgh4rQBXO2S_2Yd4Iul28-DTtY7bB0-nYdkpwHwWei1i9h3eG0nP_lhF7UxGx1sC9nKtbOBFh-71if_A0Zr8Kk1gK-sxp9hGe632ButXIKgzY18A-k7gMPXP7NKJ3CLnXYt_nSSXf96_xQ96vQQ4dldPEIXJ8dfqo_Z-uzDqnq3zgyXKmUgpdCEgNKSdqCbgsoOlDEKiq4siKbNUsi2zFsolaDKCNWaTlMBXScUcH6E3t7qTnMzQmvApaCHegp21GFXe23rfyfObureX9WSccKLYhF4eScQ_OUMMdWjjQaGQTvwc6xZLqQgVBZiQV_8h279HJYb3VBCyZwyulCvbikTfIwBur_LUFLvf6O-_xv8D4H3sfo</recordid><startdate>20210610</startdate><enddate>20210610</enddate><creator>Jang, Jaewoong</creator><creator>Song, Jaewon</creator><creator>Sim, Inae</creator><creator>Kwon, Young V.</creator><creator>Yoon, Yoosik</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9823-4555</orcidid><orcidid>https://orcid.org/0000-0002-8937-3182</orcidid></search><sort><creationdate>20210610</creationdate><title>Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between β-Catenin and NF-κB</title><author>Jang, Jaewoong ; Song, Jaewon ; Sim, Inae ; Kwon, Young V. ; Yoon, Yoosik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-e884a00e9a81feab618fe9cc9e6f760a1b9cc8d75de79419c49dcfa14eff49e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animal models</topic><topic>Bacteria</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Cytokine storm</topic><topic>Cytokines</topic><topic>Genotype & phenotype</topic><topic>Gram-negative bacteria</topic><topic>Inflammation</topic><topic>Inhibitors</topic><topic>Kidneys</topic><topic>Lipopolysaccharides</topic><topic>Liver</topic><topic>Localization</topic><topic>Lungs</topic><topic>Microscopy</topic><topic>NF-κB protein</topic><topic>Organs</topic><topic>Plasma</topic><topic>Plasma levels</topic><topic>Proteins</topic><topic>Sepsis</topic><topic>Signal transduction</topic><topic>Transcription factors</topic><topic>Wnt protein</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jang, Jaewoong</creatorcontrib><creatorcontrib>Song, Jaewon</creatorcontrib><creatorcontrib>Sim, Inae</creatorcontrib><creatorcontrib>Kwon, Young V.</creatorcontrib><creatorcontrib>Yoon, Yoosik</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jang, Jaewoong</au><au>Song, Jaewon</au><au>Sim, Inae</au><au>Kwon, Young V.</au><au>Yoon, Yoosik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between β-Catenin and NF-κB</atitle><jtitle>International journal of molecular sciences</jtitle><date>2021-06-10</date><risdate>2021</risdate><volume>22</volume><issue>12</issue><spage>6249</spage><pages>6249-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Sepsis is characterized by multiple-organ dysfunction caused by the dysregulated host response to infection. Until now, however, the role of the Wnt signaling has not been fully characterized in multiple organs during sepsis. This study assessed the suppressive effect of a Wnt signaling inhibitor, Wnt-C59, in the kidney, lung, and liver of lipopolysaccharide-induced endotoxemic mice, serving as an animal model of sepsis. We found that Wnt-C59 elevated the survival rate of these mice and decreased their plasma levels of proinflammatory cytokines and organ-damage biomarkers, such as BUN, ALT, and AST. The Wnt/β-catenin and NF-κB pathways were stimulated and proinflammatory cytokines were upregulated in the kidney, lung, and liver of endotoxemic mice. Wnt-C59, as a Wnt signaling inhibitor, inhibited the Wnt/β-catenin pathway, and its interaction with the NF-κB pathway, which resulted in the inhibition of NF-κB activity and proinflammatory cytokine expression. In multiple organs of endotoxemic mice, Wnt-C59 significantly reduced the β-catenin level and interaction with NF-κB. Our findings suggest that the anti-endotoxemic effect of Wnt-C59 is mediated via reducing the interaction between β-catenin and NF-κB, consequently suppressing the associated cytokine upregulation in multiple organs. Thus, Wnt-C59 may be useful for the suppression of the multiple-organ dysfunction during sepsis.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>34200709</pmid><doi>10.3390/ijms22126249</doi><orcidid>https://orcid.org/0000-0002-9823-4555</orcidid><orcidid>https://orcid.org/0000-0002-8937-3182</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animal models Bacteria Biomarkers Cancer Cytokine storm Cytokines Genotype & phenotype Gram-negative bacteria Inflammation Inhibitors Kidneys Lipopolysaccharides Liver Localization Lungs Microscopy NF-κB protein Organs Plasma Plasma levels Proteins Sepsis Signal transduction Transcription factors Wnt protein β-Catenin |
title | Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between β-Catenin and NF-κB |
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