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Synaptopodin is upregulated by IL-13 in eosinophilic esophagitis and regulates esophageal epithelial cell motility and barrier integrity
Mark Rochman, … , Julie M. Caldwell, Marc E. Rothenberg
Mark Rochman, … , Julie M. Caldwell, Marc E. Rothenberg
Published October 19, 2017
Citation Information: JCI Insight. 2017;2(20):e96789. https://doi.org/10.1172/jci.insight.96789.
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Research Article Gastroenterology Inflammation

Synaptopodin is upregulated by IL-13 in eosinophilic esophagitis and regulates esophageal epithelial cell motility and barrier integrity

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Abstract

Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus mediated by an IL-13–driven epithelial cell transcriptional program. Herein, we show that the cytoskeletal protein synaptopodin (SYNPO), previously associated with podocytes, is constitutively expressed in esophageal epithelium and induced during allergic inflammation. In addition, we show that the SYNPO gene is transcriptionally and epigenetically regulated by IL-13 in esophageal epithelial cells. SYNPO was expressed in the basal layer of homeostatic esophageal epithelium, colocalized with actin filaments, and expanded into the suprabasal epithelium in EoE patients, where expression was elevated 25-fold compared with control individuals. The expression level of SYNPO in esophageal biopsies correlated with esophageal eosinophil density and was improved following anti–IL-13 treatment in EoE patients. In esophageal epithelial cells, SYNPO gene silencing reduced epithelial motility in a wound healing model, whereas SYNPO overexpression impaired epithelial barrier integrity and reduced esophageal differentiation. Taken together, we demonstrate that SYNPO is induced by IL-13 in vitro and in vivo, is a nonredundant regulator of epithelial cell barrier function and motility, and is likely involved in EoE pathogenesis.

Authors

Mark Rochman, Jared Travers, J. Pablo Abonia, Julie M. Caldwell, Marc E. Rothenberg

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Figure 3

SYNPO is an actin-associated protein in esophageal epithelial cells.

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SYNPO is an actin-associated protein in esophageal epithelial cells.
(A)...
(A) Representative immunofluorescence images of SYNPO (green) in the esophageal epithelial TE-7 cell line. (B) Primary esophageal epithelial cells isolated from biopsies. DNA was labeled by Hoechst (blue), and actin was stained with phalloidin (red). The merged image shows partial colocalization of SYNPO and actin (yellow). Original magnification: ×60 (A); ×40 (B); scale bars: 10 μM.

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