| Eosinophilic esophagitis: epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment. | |
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MedLine Citation:
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PMID: 22465212 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Mechanisms underlying esophageal remodeling with subepithelial fibrosis in subjects with eosinophilic esophagitis (EoE) have not been delineated. OBJECTIVES: We sought to explore a role for epithelial mesenchymal transition (EMT) in subjects with EoE and determine whether EMT resolves with treatment. METHODS: Esophageal biopsy specimens from 60 children were immunostained for epithelial (cytokeratin) and mesenchymal (vimentin) EMT biomarkers, and EMT was quantified. Subjects studied had EoE (n = 17), indeterminate EoE (n = 15), gastroesophageal reflux disease (n = 7), or normal esophagus (n = 21). EMT was analyzed for relationships to diagnosis, eosinophil counts, and indices of subepithelial fibrosis, eosinophil peroxidase, and TGF-β immunostaining. EMT was assessed in pretreatment and posttreatment biopsy specimens from 18 subjects with EoE treated with an elemental diet, 6-food elimination diet, or topical corticosteroids (n = 6 per group). RESULTS: TGF-β1 treatment of esophageal epithelial cells in vitro for 24 hours induced upregulation of mesenchymal genes characteristic of EMT, including N-cadherin (3.3-fold), vimentin (2.1-fold), and fibronectin (7.5-fold). EMT in esophageal biopsy specimens was associated with EoE (or indeterminate EoE) but not gastroesophageal reflux disease or normal esophagus and was correlated to eosinophil counts (r = 0.691), eosinophil peroxidase (r = 0.738), and TGF-β (r = 0.520) immunostaining and fibrosis (r = 0.644) indices. EMT resolved with EoE treatments that induced clinicopathologic remission with reduced eosinophil counts. EMT decreased significantly after treatment by 74.1% overall in the 18 treated subjects with EoE; pretreatment versus posttreatment EMT scores were 3.17 ± 0.82 versus 0.82 ± 0.39 (P < .001), with similar decreases within treatment groups. Pretreatment/posttreatment EMT was strongly correlated with eosinophil counts for combined (r = 0.804, P < .001) and individual treatment groups. CONCLUSIONS: EMT likely contributes to subepithelial fibrosis in subjects with EoE and resolves with treatments that decrease esophageal inflammation, and its resolution correlates with decreased numbers of esophageal eosinophils. |
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Authors:
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Amir F Kagalwalla; Noorain Akhtar; Samantha A Woodruff; Bryan A Rea; Joanne C Masterson; Vincent Mukkada; Kalyan R Parashette; Jian Du; Sophie Fillon; Cheryl A Protheroe; James J Lee; Katie Amsden; Hector Melin-Aldana; Kelley E Capocelli; Glenn T Furuta; Steven J Ackerman |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-04-01 |
Journal Detail:
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Title: The Journal of allergy and clinical immunology Volume: 129 ISSN: 1097-6825 ISO Abbreviation: J. Allergy Clin. Immunol. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-04-30 Completed Date: 2012-07-27 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1387-1396.e7 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Department of Pediatrics, Children's Memorial Hospital and Northwestern University, Chicago, IL, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adrenal Cortex Hormones / therapeutic use Child Child, Preschool Diet Therapy Disease Progression Eosinophilic Esophagitis / pathology*, physiopathology, therapy Eosinophils / metabolism*, pathology Epithelial Cells / metabolism*, pathology Epithelial-Mesenchymal Transition* / drug effects Esophagus / drug effects, pathology* Female Humans Immunohistochemistry Infant Keratins / metabolism Male Remission Induction Transforming Growth Factor beta / metabolism Vimentin / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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K26 RR0109709/RR/NCRR NIH HHS; R21 AI079925-01/AI/NIAID NIH HHS; R21AI079925/AI/NIAID NIH HHS; UL1 RR025780/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenal Cortex Hormones; 0/Transforming Growth Factor beta; 0/Vimentin; 68238-35-7/Keratins |
| Comments/Corrections | |
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