{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:01:38Z","timestamp":1791842498793,"version":"4.3.4"},"reference-count":40,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF2016R1D1A1A02937362, 2018R1D1A1A09083263"],"award-info":[{"award-number":["NRF2016R1D1A1A02937362, 2018R1D1A1A09083263"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology and the Ministry of Science, ICT &amp; Future Planning","award":["2017R1A2B2003575"],"award-info":[{"award-number":["2017R1A2B2003575"]}]},{"name":"the Korea Health Technology R&amp;D Project","award":["HI14C0748, HI17C0387"],"award-info":[{"award-number":["HI14C0748, HI17C0387"]}]},{"name":"the Clinical Trial Center of Korea University Anam Hospital","award":["I1502411"],"award-info":[{"award-number":["I1502411"]}]},{"name":"Korea University Medical Center and Anam Hospital, Seoul, Republic of Korea","award":["K1621481, K1814581"],"award-info":[{"award-number":["K1621481, K1814581"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cleavage of E-cadherin and the resultant weakness in the cell-cell links in the laryngeal epithelium lining is induced by exposure to acidic contents of the refluxate. Herein, we aimed to evaluate the role of matrix metalloproteinases (MMPs) in inducing E-cadherin level changes following acid exposure to the human pharyngeal mucosal cells. E-cadherin levels were inversely correlated with the duration of acid exposure. Treatment with actinonin, a broad MMP inhibitor, inhibited this change. Immunocytochemical staining and transepithelial permeability test revealed that the cell surface staining of E-cadherin decreased and transepithelial permeability increased after acid exposure, which was significantly inhibited by the MMP inhibitor. Among the various MMPs analyzed, the mRNA for MMP-7 in the cellular component was upregulated, and the secretion and enzymatic activity of MMP-7 in the culture media increased with the acid treatment. Consequently, MMP-7 plays a significant role in the degradation of E-cadherin after exposure to a relatively weak acidic condition that would be similar to the physiologic condition that occurs in Laryngopharyngeal reflux disease patients.<\/jats:p>","DOI":"10.3390\/ijms20215276","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T04:41:27Z","timestamp":1571978487000},"page":"5276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Role of Matrix Metalloproteinases 7 in the Pathogenesis of Laryngopharyngeal Reflux: Decreased E-cadherin in Acid exposed Primary Human Pharyngeal Epithelial Cells"],"prefix":"10.3390","volume":"20","author":[{"given":"Nu-Ri","family":"Im","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doh Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Boramae Medical Center, Seoul 07061, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoungjae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"},{"name":"Neuroscience research institute, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Yoon","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Kuk","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/lary.1991.101.s53.1","article-title":"The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): A clinical investigation of 225 patients using ambulatory 24-h pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury","volume":"101","author":"Koufman","year":"1991","journal-title":"Laryngoscope"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0892-1997(02)00132-7","article-title":"The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers","volume":"16","author":"Hicks","year":"2002","journal-title":"J. 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