{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T12:43:36Z","timestamp":1777812216254,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T00:00:00Z","timestamp":1444694400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>The tight junction\u2013based paracellular pathway plays an important role in saliva secretion. Zonula occludens (ZO) proteins are submembranous proteins of tight junction complex; however, their function in salivary epithelium is poorly understood. Here, we found that activation of transient receptor potential vanilloid subtype 1 (TRPV1) by capsaicin increased rat saliva secretion both in vivo and ex vivo. Meanwhile, TRPV1 activation enlarged the width of tight junctions between neighboring acinar cells, increased the paracellular \ufb02ux of 4-kDa fluorescein isothiocyanate (FITC)-dextran in submandibular gland (SMG) tissues, and decreased transepithelial electric resistance (TER) in SMG-C6 cells. ZO-1, -2, and -3 were distributed principally to the apical lateral region of acinar cells in SMG tissues and continuously encircled the peripheries of SMG-C6 cells in the untreated condition. TRPV1 activation obviously diminished ZO-1 and -2 staining, but not ZO-3 or \u03b2-catenin, at the cell-cell contacts ex vivo and in vitro. Moreover, in untreated SMG-C6 cells, ZO-1 and -2 single or double knockdown by small interfering RNA (siRNA) increased the paracellular \ufb02ux of 4-kDa FITC-dextran. In capsaicin-treated cells, ZO-1 and -2 single or double knockdown abolished, whereas their re-expression restored, the capsaicin-induced increase in paracellular permeability. Furthermore, TRPV1 activation increased RhoA activity, and inhibition of either RhoA or Rho kinase (ROCK) abolished the capsaicin-induced TER decrease as well as ZO-1 and -2 redistribution. These results indicate that ZO-1 and -2 play crucial roles in both basal salivary epithelial barrier function and TRPV1-modulated paracellular transport. RhoA-ROCK signaling pathway is responsible for TRPV1-modulated paracellular permeability as well as ZO-1 and -2 redistribution.<\/jats:p>","DOI":"10.1177\/0022034515609268","type":"journal-article","created":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T22:49:16Z","timestamp":1444776556000},"page":"1748-1756","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":30,"title":["ZO-1 and -2 Are Required for TRPV1-Modulated Paracellular Permeability"],"prefix":"10.1177","volume":"94","author":[{"given":"J.","family":"Li","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"X.","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.L.","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 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