Clostridium difficile toxin A and toxin B inhibit YAP in the colonic epithelial cells
Toxin A (TcdA) and toxin B (TcdB), the two exotoxins of Clostridium difficile, are main causal agents for the colonic epithelium damage in Clostridium difficile infection (CDI). The Hippo pathway is crucial for the control of tissue homeostasis and regeneration of intestines. However, the dysregulat...
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| Veröffentlicht in: | Journal of biochemical and molecular toxicology 2021-02, Vol.35 (2), p.e22652-n/a |
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| creator | Song, Jinglue Shen, Xia Huang, Zhenyu Liu, Yun Cui, Long Cui, Xuewei Liu, Chen‐Ying |
| description | Toxin A (TcdA) and toxin B (TcdB), the two exotoxins of Clostridium difficile, are main causal agents for the colonic epithelium damage in Clostridium difficile infection (CDI). The Hippo pathway is crucial for the control of tissue homeostasis and regeneration of intestines. However, the dysregulation of Hippo pathway in CDI is unclear. Here we show that YAP and TAZ, the transcriptional coactivators downstream of the Hippo pathway, are sequestered in the cytoplasm, degraded, and inactivated by treatment with TcdA and TcdB in colonic epithelial cells. The overexpression of YAP restores the messenger RNA expressions of YAP target genes, attenuates the disruption of cytoskeleton and cell rounding, and rescues the cell proliferation of colonic epithelial cells under exposure of the two toxins. Our results demonstrate that inhibition of YAP and TAZ is involved in the pathogenesis of CDI, implicating that increasing YAP activity could be a potential therapeutic strategy for the CDI treatment. |
| doi_str_mv | 10.1002/jbt.22652 |
| format | Article |
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The Hippo pathway is crucial for the control of tissue homeostasis and regeneration of intestines. However, the dysregulation of Hippo pathway in CDI is unclear. Here we show that YAP and TAZ, the transcriptional coactivators downstream of the Hippo pathway, are sequestered in the cytoplasm, degraded, and inactivated by treatment with TcdA and TcdB in colonic epithelial cells. The overexpression of YAP restores the messenger RNA expressions of YAP target genes, attenuates the disruption of cytoskeleton and cell rounding, and rescues the cell proliferation of colonic epithelial cells under exposure of the two toxins. Our results demonstrate that inhibition of YAP and TAZ is involved in the pathogenesis of CDI, implicating that increasing YAP activity could be a potential therapeutic strategy for the CDI treatment.</description><identifier>ISSN: 1095-6670</identifier><identifier>EISSN: 1099-0461</identifier><identifier>DOI: 10.1002/jbt.22652</identifier><identifier>PMID: 33251692</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Cell proliferation ; Clostridium difficile ; Cytoplasm ; Cytoskeleton ; Epithelial cells ; Epithelium ; Exotoxins ; Homeostasis ; Intestine ; mRNA ; Pathogenesis ; Regeneration ; Rounding ; TAZ ; Toxin A ; Toxin B ; Toxins ; Transcription ; YAP ; Yes-associated protein</subject><ispartof>Journal of biochemical and molecular toxicology, 2021-02, Vol.35 (2), p.e22652-n/a</ispartof><rights>2020 Wiley Periodicals LLC</rights><rights>2020 Wiley Periodicals LLC.</rights><rights>2021 Wiley Periodicals LLC</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-57cbdfea2999662b2176f9b1821b9e90481bc69a4fea185f020f4180d3c67e6c3</citedby><cites>FETCH-LOGICAL-c3532-57cbdfea2999662b2176f9b1821b9e90481bc69a4fea185f020f4180d3c67e6c3</cites><orcidid>0000-0002-0160-8638</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbt.22652$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbt.22652$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33251692$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Jinglue</creatorcontrib><creatorcontrib>Shen, Xia</creatorcontrib><creatorcontrib>Huang, Zhenyu</creatorcontrib><creatorcontrib>Liu, Yun</creatorcontrib><creatorcontrib>Cui, Long</creatorcontrib><creatorcontrib>Cui, Xuewei</creatorcontrib><creatorcontrib>Liu, Chen‐Ying</creatorcontrib><title>Clostridium difficile toxin A and toxin B inhibit YAP in the colonic epithelial cells</title><title>Journal of biochemical and molecular toxicology</title><addtitle>J Biochem Mol Toxicol</addtitle><description>Toxin A (TcdA) and toxin B (TcdB), the two exotoxins of Clostridium difficile, are main causal agents for the colonic epithelium damage in Clostridium difficile infection (CDI). 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Our results demonstrate that inhibition of YAP and TAZ is involved in the pathogenesis of CDI, implicating that increasing YAP activity could be a potential therapeutic strategy for the CDI treatment.</description><subject>Cell proliferation</subject><subject>Clostridium difficile</subject><subject>Cytoplasm</subject><subject>Cytoskeleton</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Exotoxins</subject><subject>Homeostasis</subject><subject>Intestine</subject><subject>mRNA</subject><subject>Pathogenesis</subject><subject>Regeneration</subject><subject>Rounding</subject><subject>TAZ</subject><subject>Toxin A</subject><subject>Toxin B</subject><subject>Toxins</subject><subject>Transcription</subject><subject>YAP</subject><subject>Yes-associated protein</subject><issn>1095-6670</issn><issn>1099-0461</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp10E1LwzAcBvAgipvTg19AAl70UJekTdIct-ErAz1sB0-lTROWkTazadF9e7N1ehA85Qn8ePjzAHCJ0R1GiIzXRXtHCKPkCAwxEiJCCcPH-0wjxjgagDPv1wghKjg9BYM4JhQzQYZgObPOt40pTVfB0mhtpLEKtu7L1HAC87o85Ck09coUpoXvk7eQYbtSUDrraiOh2pjwtSa3UCpr_Tk40bn16uLwjsDy4X4xe4rmr4_Ps8k8kjGNSUS5LEqtciKEYIwUBHOmRYFTgguhBEpSXEgm8iQYnFKNCNIJTlEZS8YVk_EI3PS9m8Z9dMq3WWX87oK8Vq7zGUkY5ZRhEQd6_YeuXdfU4bqgUo4EJ5QGddsr2TjvG6WzTWOqvNlmGGW7rbOwdbbfOtirQ2NXVKr8lT_jBjDuwWeYdPt_U_YyXfSV31AOhmo</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Song, Jinglue</creator><creator>Shen, Xia</creator><creator>Huang, Zhenyu</creator><creator>Liu, Yun</creator><creator>Cui, Long</creator><creator>Cui, Xuewei</creator><creator>Liu, Chen‐Ying</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0160-8638</orcidid></search><sort><creationdate>202102</creationdate><title>Clostridium difficile toxin A and toxin B inhibit YAP in the colonic epithelial cells</title><author>Song, Jinglue ; Shen, Xia ; Huang, Zhenyu ; Liu, Yun ; Cui, Long ; Cui, Xuewei ; Liu, Chen‐Ying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-57cbdfea2999662b2176f9b1821b9e90481bc69a4fea185f020f4180d3c67e6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cell proliferation</topic><topic>Clostridium difficile</topic><topic>Cytoplasm</topic><topic>Cytoskeleton</topic><topic>Epithelial cells</topic><topic>Epithelium</topic><topic>Exotoxins</topic><topic>Homeostasis</topic><topic>Intestine</topic><topic>mRNA</topic><topic>Pathogenesis</topic><topic>Regeneration</topic><topic>Rounding</topic><topic>TAZ</topic><topic>Toxin A</topic><topic>Toxin B</topic><topic>Toxins</topic><topic>Transcription</topic><topic>YAP</topic><topic>Yes-associated protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Song, Jinglue</creatorcontrib><creatorcontrib>Shen, Xia</creatorcontrib><creatorcontrib>Huang, Zhenyu</creatorcontrib><creatorcontrib>Liu, Yun</creatorcontrib><creatorcontrib>Cui, Long</creatorcontrib><creatorcontrib>Cui, Xuewei</creatorcontrib><creatorcontrib>Liu, Chen‐Ying</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biochemical and molecular toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Jinglue</au><au>Shen, Xia</au><au>Huang, Zhenyu</au><au>Liu, Yun</au><au>Cui, Long</au><au>Cui, Xuewei</au><au>Liu, Chen‐Ying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clostridium difficile toxin A and toxin B inhibit YAP in the colonic epithelial cells</atitle><jtitle>Journal of biochemical and molecular toxicology</jtitle><addtitle>J Biochem Mol Toxicol</addtitle><date>2021-02</date><risdate>2021</risdate><volume>35</volume><issue>2</issue><spage>e22652</spage><epage>n/a</epage><pages>e22652-n/a</pages><issn>1095-6670</issn><eissn>1099-0461</eissn><abstract>Toxin A (TcdA) and toxin B (TcdB), the two exotoxins of Clostridium difficile, are main causal agents for the colonic epithelium damage in Clostridium difficile infection (CDI). The Hippo pathway is crucial for the control of tissue homeostasis and regeneration of intestines. However, the dysregulation of Hippo pathway in CDI is unclear. Here we show that YAP and TAZ, the transcriptional coactivators downstream of the Hippo pathway, are sequestered in the cytoplasm, degraded, and inactivated by treatment with TcdA and TcdB in colonic epithelial cells. The overexpression of YAP restores the messenger RNA expressions of YAP target genes, attenuates the disruption of cytoskeleton and cell rounding, and rescues the cell proliferation of colonic epithelial cells under exposure of the two toxins. 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| subjects | Cell proliferation Clostridium difficile Cytoplasm Cytoskeleton Epithelial cells Epithelium Exotoxins Homeostasis Intestine mRNA Pathogenesis Regeneration Rounding TAZ Toxin A Toxin B Toxins Transcription YAP Yes-associated protein |
| title | Clostridium difficile toxin A and toxin B inhibit YAP in the colonic epithelial cells |
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