Document Detail


Eosinophilic esophagitis: epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment.
MedLine Citation:
PMID:  22465212     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-01
Journal Detail:
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:
Created Date:  2012-04-30     Completed Date:  2012-07-27     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1387-1396.e7     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Department of Pediatrics, Children's Memorial Hospital and Northwestern University, Chicago, IL, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
0/Adrenal Cortex Hormones; 0/Transforming Growth Factor beta; 0/Vimentin; 68238-35-7/Keratins
Comments/Corrections

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