RT Journal Article
T1 Proteomic analysis of the esophageal epithelium reveals key features of eosinophilic esophagitis pathophysiology
A1 Molina Jiménez, Francisca
A1 Ugalde Triviño, Lola
A1 Arias González, Laura
A1 Relaño Rupérez, Carlos
A1 Casabona, Sergio
A1 Pérez Fernández, María Teresa
A1 Martín Domínguez, Verónica
A1 Fernández Pacheco, Jennifer
A1 Laserna Mendieta, Emilio José
A1 Muñoz Hernández, Patricia
A1 Arias Arias, Ángel
A1 Cano, Ainara
A1 Muñoz, Javier
A1 Lucendo, Alfredo J.
A1 Santander, Cecilio
A1 Majano, Pedro
A1 Majano Rodríguez, Pedro Lorenzo
AB BackgroundEosinophilic 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.MethodsTotal 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).ResultsA 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.ConclusionsWe 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.
PB Wiley
SN 0105-4538
YR 2023
FD 2023-10
LK https://hdl.handle.net/20.500.14352/102911
UL https://hdl.handle.net/20.500.14352/102911
LA eng
NO European Regional Development Fund
NO Ministerio de Ciencia e Innovación (MCIN)
NO Ministerio de Trabajo y Economía Social
NO Comunidad de Madrid
NO Asociacion Española de Gastroenterología
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 10 abr 2025