{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:29Z","timestamp":1787028509180,"version":"build-2736575974"},"reference-count":118,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Reckitt Benckiser UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epithelial barrier dysfunction is a hallmark of gastroesophageal reflux disease (GERD) related to symptom origination, inflammatory remodeling and carcinogenesis. Alginate-based antireflux medications were previously shown to topically protect against peptic barrier disruption, yet the molecular mechanisms of injury and protection were unclear. Herein, Barrett\u2019s esophageal (BAR-T) cells were pretreated with buffered saline (HBSS; control), dilute alginate medications (Gaviscon Advance or Gaviscon Double Action, Reckitt Benckiser), a viscosity-matched placebo, or ADAM10 and matrix metalloproteinase (MMP) inhibitors before exposure to HBSS pH7.4 or pH4 \u00b1 1 mg\/mL pepsin for 10\u201360 min. Cell viability was assessed by ATP assay; mediators of epithelial integrity, E-cadherin, ADAM10, and MMPs were examined by Western blot and qPCR. Alginate rescued peptic reduction of cell viability (p &lt; 0.0001). Pepsin-pH4 yielded E-cadherin fragments indicative of regulated intramembrane proteolysis (RIP) which was not rescued by inhibitors of known E-cadherin sheddases. Transcriptional targets of E-cadherin RIP fragments were elevated at 24 h (MMP-1,2,9,14; p &lt; 0.01). Alginate rescued E-cadherin cleavage, ADAM10 maturation, and MMP induction (p &lt; 0.01). Results support RIP as a novel mechanism of peptic injury during GERD. Alginate residue after wash-out to mimic physiologic esophageal clearance conferred lasting protection against pepsin-induced molecular mechanisms that may exacerbate GERD severity and promote carcinogenesis in the context of weakly acidic reflux.<\/jats:p>","DOI":"10.3390\/ijms24097932","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T04:30:47Z","timestamp":1682569847000},"page":"7932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Topical Alginate Protection against Pepsin-Mediated Esophageal Damage: E-Cadherin Proteolysis and Matrix Metalloproteinase Induction"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7045-357X","authenticated-orcid":false,"given":"Tina L.","family":"Samuels","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-1409","authenticated-orcid":false,"given":"Simon","family":"Blaine-Sauer","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6599-4622","authenticated-orcid":false,"given":"Ke","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Quantitative Health Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-8605","authenticated-orcid":false,"given":"Kate","family":"Plehhova","sequence":"additional","affiliation":[{"name":"Reckitt Benckiser, Hull HU8 7DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathal","family":"Coyle","sequence":"additional","affiliation":[{"name":"Reckitt Benckiser, Hull HU8 7DS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1136\/gutjnl-2012-304269","article-title":"Update on the Epidemiology of Gastro-Oesophageal Reflux Disease: A Systematic Review","volume":"63","author":"Sweet","year":"2014","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/j.gastro.2017.07.045","article-title":"Presentation and Epidemiology of Gastroesophageal Reflux disease","volume":"154","author":"Richter","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1136\/gutjnl-2016-313589","article-title":"Global Prevalence of, and Risk Factors for, Gastro-Oesophageal Reflux Symptoms: A Meta-Analysis","volume":"67","author":"Eusebi","year":"2018","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5814","DOI":"10.1038\/s41598-020-62795-1","article-title":"Global Prevalence and Risk Factors of Gastro-Oesophageal Reflux Disease (Gord): Systematic Review with Meta-Analysis","volume":"10","author":"Nirwan","year":"2020","journal-title":"Sci. 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