Cripto-1 Is Elevated In Pediatric Subjects With Eosinophilic Esophagitis

Abstract

RationaleEosinophilic esophagitis (EoE) is a chronic antigen mediated allergic response leading to tissue remodeling that includes basal zone hyperplasia and fibrosis in both pediatric and adult patients. Cripto-1, a member of the CFC-EGF family, is known to induce epithelial to mesenchymal transition (EMT) and epithelial cell proliferation. The role of Cripto-1 in EoE has yet to be characterized.MethodsImmunohistochemistry and qPCR were utilized to quantitate Cripto-1 and its receptor, Glypican-1, in biopsies and cultured primary esophageal epithelial cells from pediatric EoE and non-diseased control subjects.ResultsImmunohistochemistry and quantitative image analysis using a Cripto-1 specific antibody on paraffin-embedded specimens from active EoE subjects (n= 43) and non-diseased controls (n= 6) demonstrated elevated Cripto-1 in the epithelium of EoE patients compared to normal (p= 0.0005). Elevated Cripto-1 in the epithelium correlated with epithelial basal zone hyperplasia (rs=0.80, p= 0.0001). In addition, immunohistochemistry and quantitative PCR confirmed the presence of the Cripto-1 receptor, Glypican-1, in both paraffin-embedded specimens and cultured primary esophageal epithelial cells from EoE patients.ConclusionsPediatric EoE subjects have elevated epithelial Cripto-1 compared to control which may allude to a mechanistic pathway in which the signaling molecule binds to its receptor, Glypican-1, and has downstream effects contributing to tissue remodeling. RationaleEosinophilic esophagitis (EoE) is a chronic antigen mediated allergic response leading to tissue remodeling that includes basal zone hyperplasia and fibrosis in both pediatric and adult patients. Cripto-1, a member of the CFC-EGF family, is known to induce epithelial to mesenchymal transition (EMT) and epithelial cell proliferation. The role of Cripto-1 in EoE has yet to be characterized. Eosinophilic esophagitis (EoE) is a chronic antigen mediated allergic response leading to tissue remodeling that includes basal zone hyperplasia and fibrosis in both pediatric and adult patients. Cripto-1, a member of the CFC-EGF family, is known to induce epithelial to mesenchymal transition (EMT) and epithelial cell proliferation. The role of Cripto-1 in EoE has yet to be characterized. MethodsImmunohistochemistry and qPCR were utilized to quantitate Cripto-1 and its receptor, Glypican-1, in biopsies and cultured primary esophageal epithelial cells from pediatric EoE and non-diseased control subjects. Immunohistochemistry and qPCR were utilized to quantitate Cripto-1 and its receptor, Glypican-1, in biopsies and cultured primary esophageal epithelial cells from pediatric EoE and non-diseased control subjects. ResultsImmunohistochemistry and quantitative image analysis using a Cripto-1 specific antibody on paraffin-embedded specimens from active EoE subjects (n= 43) and non-diseased controls (n= 6) demonstrated elevated Cripto-1 in the epithelium of EoE patients compared to normal (p= 0.0005). Elevated Cripto-1 in the epithelium correlated with epithelial basal zone hyperplasia (rs=0.80, p= 0.0001). In addition, immunohistochemistry and quantitative PCR confirmed the presence of the Cripto-1 receptor, Glypican-1, in both paraffin-embedded specimens and cultured primary esophageal epithelial cells from EoE patients. Immunohistochemistry and quantitative image analysis using a Cripto-1 specific antibody on paraffin-embedded specimens from active EoE subjects (n= 43) and non-diseased controls (n= 6) demonstrated elevated Cripto-1 in the epithelium of EoE patients compared to normal (p= 0.0005). Elevated Cripto-1 in the epithelium correlated with epithelial basal zone hyperplasia (rs=0.80, p= 0.0001). In addition, immunohistochemistry and quantitative PCR confirmed the presence of the Cripto-1 receptor, Glypican-1, in both paraffin-embedded specimens and cultured primary esophageal epithelial cells from EoE patients. ConclusionsPediatric EoE subjects have elevated epithelial Cripto-1 compared to control which may allude to a mechanistic pathway in which the signaling molecule binds to its receptor, Glypican-1, and has downstream effects contributing to tissue remodeling. Pediatric EoE subjects have elevated epithelial Cripto-1 compared to control which may allude to a mechanistic pathway in which the signaling molecule binds to its receptor, Glypican-1, and has downstream effects contributing to tissue remodeling.