Eosinophilic esophagitis: epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment.
Eosinophilic esophagitis: epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment.
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DOI：
10.1016/j.jaci.2012.03.005
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Ackerman SJ
中科院分区：
文献类型：
--
作者：
Kagalwalla AF;Akhtar N;Woodruff SA;Rea BA;Masterson JC;Mukkada V;Parashette KR;Du J;Fillon S;Protheroe CA;Lee JJ;Amsden K;Melin-Aldana H;Capocelli KE;Furuta GT;Ackerman SJ
Mechanisms underlying esophageal remodeling with subepithelial fibrosis in eosinophilic esophagitis (EoE) have not been delineated. To explore a role for Epithelial Mesenchymal Transition (EMT) in EoE, and whether EMT resolves with treatment. Esophageal biopsies from 60 children were immunostained for epithelial (cytokeratin) and mesenchymal (vimentin) EMT biomarkers, and EMT quantified. Subjects studied had EoE (n=17), EoE-indeterminate (n=15), GERD (n=7) or normal esophagus (n=21). EMT was analyzed for relationships to diagnosis, eosinophils, and indices of subepithelial fibrosis, eosinophil peroxidase (EPX) and TGF-β immunostaining. EMT was assessed in pre- and post-treatment biopsies from 18 EoE subjects treated with elemental diet, six-food elimination diet, or topical corticosteroids (n=6/group). TGF-β1 treatment of esophageal epithelial cells in vitro for 24hrs 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 biopsies was associated with EoE (or indeterminate EoE), but not GERD or normal esophagus, and was correlated to eosinophils (r=0.691), EPX (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 eosinophils. EMT decreased significantly post-treatment by 74.1% overall in the 18 treated EoE subjects; pre- vs. post-treatment EMT scores–3.17±0.82 vs. 0.82±0.39 (p<0.001), with similar decreases within treatment groups. Pre-/post-treatment EMT was strongly correlated with eosinophils for combined (r=0.804, p< 0.001) and individual treatment groups. EMT likely contributes to subepithelial fibrosis in EoE, resolves with treatments that decrease esophageal inflammation, and its resolution correlates with decreased numbers of esophageal eosinophils.
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