Mechanisms of allergy and clinical immunologyEosinophilic esophagitis: Epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment
Section snippets
Cell culture and induction of EMT in vitro
Human esophageal epithelial HET-1A cells (American Type Culture Collection, Manassas, Va) were maintained in Bronchial Epithelial Growth Media without gentamycin-amphotericin B (Lonza/Clonetics, Walkersville, Md). For mRNA analysis, cells at confluence in 6-well plates were cultured an additional 24 or 48 hours in fresh media with or without 5 ng/mL TGF-β1 (R&D Systems, Minneapolis, Minn). Expression of mRNAs encoding adhesion and cytoskeletal proteins representative of epithelial cells
EMT is induced by TGF-β in cultured esophageal epithelial cells
To determine whether esophageal epithelium has the capacity to undergo EMT, we analyzed the ability of TGF-β1 to induce EMT in vitro in the HET-1A esophageal epithelial cell line. Culture of HET-1A cells with TGF-β1 decreased gene transcription for epithelial biomarkers, including adhesion proteins and cytoskeletal components representative of the epithelial phenotypes cytokeratin 8 (22% decrease, P < .01) and cytokeratin 14 (44% decrease, P = .27; Fig 2). Correspondingly, increased mRNA
Discussion
Because esophageal tissue can demonstrate significant epithelial basal zone hyperplasia and subepithelial fibrosis in subjects with EoE, we hypothesized that EMT might be one of the processes associated with these remodeling events. Our results identified the presence of EMT in children with active EoE and showed that treatments that resolve eosinophilic inflammation and epithelial hyperplasia reverse EMT and subepithelial fibrosis. We also showed that the degree of EMT and its resolution in
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2022, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Additionally, we found that select EAPs captured by the EST (EDN and CLC/Gal-10) correlate significantly and negatively with esophageal distensibility (ρ −0.44 and ρ −0.47, respectively (P < .01) (Table II). In the setting of chronic inflammation, epithelial cells take on characteristics of mesenchymal cells (fibroblasts, myofibroblasts), expressing collagens and vimentin and losing their epithelial cadherins (E-cadherin).1,15,21,22 These changes in the epithelium contribute to esophageal remodeling.
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Supported in part by a translational research award from the AGA (to S.J.A. and G.T.F.), National Institutes of Health (NIH) grant R21AI079925 (to G.T.F. and S.J.A.), unrestricted gifts from the Campaign Urging Research on Eosinophilic Diseases (CURED; to S.J.A., G.T.F., and A.F.K.) and the Buckeye Foundation (to A.F.K.), and research funds from the UIC Department of Pediatrics (to A.F.K. and S.J.A.) and the Mayo Foundation and its NIH grant NCRR K26 RR0109709 (J.J.L.). B.A.R. was supported in part by a Craig Medical Student Summer Research Fellowship from the UIC COM. The CURED and Buckeye Foundations did not play any role in development of the study or in the preparation of this manuscript aside from providing research funding. This project was also supported in part by NIH/NCRR Colorado CTSI grant UL1 RR025780 (to G.T.F., S.A.W., and J.C.M.). Its contents are the authors' sole responsibility and do not necessarily represent official NIH views. S.J.A. and G.T.F. are members of the Medical Advisory Panel of the American Partnership for Eosinophilic Diseases.
Disclosure of potential conflict of interest: A. F. Kagalwalla is on the speakers' bureau for Abbott Nutrition and has received research support from the Campaign Urging Research on Eosinophil Diseases, the Buckeye Foundation, and the University of Illinois at Chicago Department of Pediatrics. G. T. Furuta has received research support from the American Gastroenterological Association. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.
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These authors were co-senior authors.
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S. A. Woodruff is currently at the University of Massachusetts Memorial Medical Center, Pediatric Gastroenterology and Nutrition, Worcester, Mass, and V. Mukkada is currently at Pediatric Gastroenterology, Nutrition, and Liver Diseases, Pediatric Food Allergy Program, Hasbro Children's Hospital, Alpert Medical School, Brown University, Providence, RI.