Reduction of E-cadherin by human defensin-5 in esophageal squamous cells |
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Authors: | Yoshiki Nomura Hiroki Tanabe Kentaro Moriichi Satomi Igawa Katsuyoshi Ando Nobuhiro Ueno Shin Kashima Motoya Tominaga Takuma Goto Yuhei Inaba Takahiro Ito Akemi Ishida-Yamamoto Mikihiro Fujiya Yutaka Kohgo |
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Affiliation: | 1. Division of Gastroenterology and Hepatology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan;2. Department of Dermatology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan |
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Abstract: | Barrett’s esophagus (BE) is metaplastic columnar epithelium converted from normal squamous epithelia in the distal esophagus that is thought to be a precancerous lesion of esophageal adenocarcinoma. BE is attributed to gastroesophageal reflux disease (GERD), and therefore gastric acid or bile acids are thought to be factors that cause epithelial cell damage and inflammation in the gastro-esophageal junction. The decrease of adherent junction molecules, E-cadherin has been reported to be associated with the progression of the Barrett’s carcinoma, but the initiation of BE is not sufficiently understood. BE is characterized by the presence of goblet cells and occasionally Paneth cells are observed at the base of the crypts. The Paneth cells possess dense granules, in which human antimicrobial peptide human defensin-5 (HD-5) are stored and secreted out of the cells. This study determined the roles of HD-5 produced from metaplastic Paneth cells against adjacent to squamous cells in the gastro-esophageal junction. A human squamous cell line Het-1A, was incubated with the synthetic HD-5 peptide as a model of squamous cell in the gastro-esophageal junctions, and alterations of E-cadherin were investigated. Immunocytochemistry, flowcytometry, and Western blotting showed that the expression of E-cadherin protein was decreased. And a partial recovery from the decrease was observed by treatment with a CD10/neprilysin inhibitor (thiorphan). In conclusion, E-cadherin expression in squamous cells was reduced by HD-5 using in vitro experiments. In gastro-esophageal junction, HD-5 produced from metaplastic Paneth cells may therefore accelerate the initiation of BE. |
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Keywords: | Barrett&rsquo s esophagus Antimicrobial peptide Cytoskeleton Regeneration |
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