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Proteomic Analysis of Eosinophilic Esophagitis: Identification and Involvement of the Minichromosome Maintenance Complex as a Driver of Esophageal Basal Zone Hyperplasia

ABSTRACT: To uncover molecular drivers of Eosinophilic Esophagitis (EoE), a global proteome screen of the esophageal biopsies from individuals with and without EoE was performed.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Eosinophilic Esophagitis

SUBMITTER: Aleksandra Nita-Lazar

LAB HEAD: Aleksandra Nita-Lazar

PROVIDER: PXD040030 | Pride | 2023-08-01

REPOSITORIES: Pride

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			Action	DRS
	01_EoE1.raw	Raw
	02_NL1.raw	Raw
	03_NL2.raw	Raw
	04_EoE2.raw	Raw
	05_NL3.raw	Raw

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The minichromosome maintenance complex drives esophageal basal zone hyperplasia.

Project description:Eosinophilic esophagitis (EoE) is a chronic gastrointestinal disorder characterized by food antigen-driven eosinophilic inflammation and hyperproliferation of esophageal mucosa. By utilizing a large-scale, proteomic screen of esophageal biopsies, we aimed to uncover molecular drivers of the disease. Proteomic analysis by liquid chromatography-tandem mass spectrometry identified 402 differentially expressed proteins (DEPs) that correlated with the EoE transcriptome. Immune cell-related proteins were among the most highly upregulated DEPs in EoE compared with controls, whereas proteins linked to epithelial differentiation were primarily downregulated. Notably, in the inflamed esophageal tissue, all 6 subunits of the minichromosome maintenance (MCM) complex, a DNA helicase essential for genomic DNA replication, were significantly upregulated at the gene and protein levels. Furthermore, treating esophageal epithelial cells with a known inhibitor of the MCM complex (ciprofloxacin) blocked esophageal epithelial proliferation. In a murine model of EoE driven by overexpression of IL-13, ciprofloxacin treatment decreased basal zone thickness and reduced dilated intercellular spaces by blocking the transition of epithelial cells through the S-phase of the cell cycle. Collectively, a broad-spectrum proteomic screen has identified the involvement of the MCM complex in EoE and has highlighted MCM inhibitors as potential therapeutic agents for the disease.

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