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We\u2019ve previously reported compromised epithelial barrier integrity in a toluene diisocyanate (TDI)-induced occupational asthma model. This study is aimed to explore the role of transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential ankyrin 1 (TRPA1) in the dysfunction of adherens junctions in TDI-induced asthma. Mice were sensitized and challenged with TDI for a chemical-induced asthma model. Selective blockers of TRPV4 glycogen synthase kinase (GSK)2193874, 5 and 10 mg\/kg) and TRPA1 (HC030031, 10 and 20 mg\/kg) were intraperitoneally given to the mice. Immunohistochemistry revealed different expression pattern of TRPV4 and TRPA1 in lung. TDI exposure increased TRPV4 expression in the airway, which can be suppressed by GSK2193874, while treatment with neither TDI alone nor TDI together with HC030031 led to changes of TRPA1 expression in the lung. Blocking either TRPV4 or TRPA1 blunted TDI-induced airway hyperreactivity, airway neutrophilia and eosinophilia, as well as Th2 responses in a dose-dependent manner. At the same time, membrane levels of E-cadherin and \u03b2-catenin were significantly decreased after TDI inhalation, which were inhibited by GSK2193874 or HC030031. Moreover, GSK2193874 and HC030031 also suppressed serine phosphorylation of glycogen synthase kinase 3\u03b2, tyrosine phosphorylation of \u03b2-catenin, as well as activation and nuclear transport of \u03b2-catenin in mice sensitized and challenged with TDI. Our study suggested that both TRPV4 and TRPA1 contribute critically to E-cadherin and \u03b2-catenin dysfunction in TDI-induced asthma, proposing novel therapeutic targets for asthma.<\/jats:p>","DOI":"10.1093\/toxsci\/kfy285","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T08:18:30Z","timestamp":1543479510000},"page":"160-170","source":"Crossref","is-referenced-by-count":33,"title":["Transient Receptor Potential Ion Channels Mediate Adherens Junctions Dysfunction in a Toluene Diisocyanate-Induced Murine Asthma Model"],"prefix":"10.1093","volume":"168","author":[{"given":"Lihong","family":"Yao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510180, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixiong","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Minzu Hospital of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning 530001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peikai","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510180, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shushan","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510180, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyu","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Respirology, Department of Medicine, McMaster University, Firestone Institute for Respiratory Health (FIRH), The Research Institution of St. Joe's Hamilton (RISH), St. Joseph's Healthcare, Hamilton, ON L8N 4A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ailin","family":"Tao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510180, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongchang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingling","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510180, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"2019091111282901500_kfy285-B1","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1161\/01.RES.0000247065.11756.19","article-title":"Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: A novel mechanism of acute lung injury","volume":"99","author":"Alvarez","year":"2006","journal-title":"Circ. 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