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Title: Proteomic analysis of the esophageal epithelium reveals key features of eosinophilic esophagitis pathophysiology
Authors: Molina-Jimenez, Francisca; Ugalde-Trivino, Lola; Arias-Gonzalez, Laura; Relano-Ruperez, Carlos; Casabona, Sergio; Teresa Perez-Fernandez, Maria; Martin-Dominguez, Veronica; Fernandez-Pacheco, Jennifer; Jose Laserna-Mendieta, Emilio; Munoz-Hernandez, Patricia; Arias-Arias, Angel; Cano, Ainara; Munoz, Javier; Lucendo, Alfredo J.; Santander, Cecilio; Majano, Pedro
Citation: ALLERGY, 2023, 78, 2732-2744
Abstract: Background: Eosinophilic esophagitis (EoE) is a chronic non-IgE-mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal epithelium. Additionally, an RNAseq-based transcriptomic analysis in paired samples was also carried out. Methods: Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE-specific mRNA panels (EDP and Eso-EoE panel). Results: A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA-proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil-related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome. Conclusions: We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms.
Keywords: basic mechanisms; eosinophilic esophagitis; epithelium; proteomic; EXPRESSION; DIAGNOSIS; GUIDELINES; MANAGEMENT; SYMPTOMS; FIBROSIS; THERAPY; HEALTH
Issue Date: 2023
Publisher: WILEY
Type: Article; Early Access
DOI: 10.1111/all.15779
ISSN: 0105-4538
E-ISSN: 1398-9995
Funder: Asociacion Espanola Gastroenterologia [09-PIN1-00015.6/2022]
Comunidad de Madrid
European Regional Development Fund
Instituto de Salud Carlos III [PI17/0008, JR19/00005]
Ministerio de Ciencia e Innovacion [PID2021-123144OB-I00]
Ministerio de Trabajo y Economia Social
Appears in Publication types:Artículos científicos

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