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Both TRPV1 and occludin were expressed in SMG-C6 cells, and capsaicin induced redistribution of occludin, but not claudin-3, claudin-4 or E-cadherin, from the cell membrane into the cytoplasm. Capsaicin also decreased transepithelial electrical resistance (TER) and increased the Trypan Blue and FITC\u2013dextran flux. Capsazepine (CPZ), a TRPV1 antagonist, inhibited the capsaicin-induced occludin redistribution and TER decrease. Moreover, occludin knockdown by shRNA suppressed, whereas occludin re-expression restored, the TER response to capsaicin. Mechanistically, TRPV1 activation increased ERK1\/2 and MLC2 phosphorylation. PD98059, an ERK1\/2 kinase inhibitor, abolished the capsaicin-induced MLC2 phosphorylation, whereas ML-7, an MLC2 kinase inhibitor, did not affect ERK1\/2 phosphorylation, suggesting that ERK1\/2 is the upstream signaling molecule of MLC2. Capsaicin also induced F-actin reorganization, which was abolished by CPZ, PD98059 and ML-7, indicating that TRPV1 activation altered F-actin organization in an ERK1\/2- and MLC2-dependent manner. Furthermore, either PD98059 or ML-7 could abolish the capsaicin-induced TER response and occludin redistribution, whereas knockdown of ERK1\/2 further confirmed that the TRPV1-modulated paracellular permeability was ERK1\/2 dependent. Taken together, these results identified a crucial role of occludin in submandibular epithelial cells, and more importantly, demonstrated that occludin was required to mediate TRPV1-modulated paracellular permeability.<\/jats:p>","DOI":"10.1242\/jcs.111781","type":"journal-article","created":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T10:14:23Z","timestamp":1359022463000},"page":"1109-1121","source":"Crossref","is-referenced-by-count":39,"title":["Occludin is required for TRPV1-modulated paracellular permeability in the submandibular gland"],"prefix":"10.1242","volume":"126","author":[{"given":"Xin","family":"Cong","sequence":"first","affiliation":[{"name":"Center for Salivary Gland Diseases of Peking University School and Hospital of Stomatology, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Salivary Gland Diseases of Peking University School and Hospital of Stomatology, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning-Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Ding","sequence":"additional","affiliation":[{"name":"Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Wen","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Dental Emergency, Beijing Stomatological Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Chao","family":"Su","sequence":"additional","affiliation":[{"name":"Center for Salivary Gland Diseases of Peking University School and Hospital of Stomatology, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hong","family":"Guo","sequence":"additional","affiliation":[{"name":"Center for Salivary Gland Diseases of Peking University School and Hospital of Stomatology, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ling","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Salivary Gland Diseases of Peking University School and Hospital of Stomatology, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Yan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021111216263783900_b1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.bbrc.2004.06.149","article-title":"Transient receptor potential vanilloid subfamily 1 expressed in pancreatic islet beta cells modulates insulin secretion in rats.","volume":"321","author":"Akiba","year":"2004","journal-title":"Biochem. 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