{"doi":"10.1172/jci.insight.172143","title":"The minichromosome maintenance complex drives esophageal basal zone hyperplasia","abstract":"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.","journal":"JCI Insight","year":2023,"id":348163,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9472,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1049831,"name":"Yrina Rochman","orcid":"0000-0002-1129-5946","position":1,"is_corresponding":false},{"id":349886,"name":"Julie M. Caldwell","orcid":"0000-0002-3855-299X","position":2,"is_corresponding":false},{"id":349885,"name":"Lydia E. Mack","orcid":"0000-0003-4154-9297","position":3,"is_corresponding":false},{"id":863306,"name":"John A. Besse","orcid":"0000-0002-9874-5822","position":4,"is_corresponding":false},{"id":400351,"name":"Nathan P. Manes","orcid":"0000-0001-6701-3314","position":5,"is_corresponding":false},{"id":267563,"name":"Sung Hwan Yoon","orcid":"0000-0001-5794-3286","position":6,"is_corresponding":false},{"id":445119,"name":"Tetsuo Shoda","orcid":"0000-0001-8337-5438","position":7,"is_corresponding":false},{"id":400352,"name":"Aleksandra Nita‐Lazar","orcid":"0000-0002-8523-605X","position":8,"is_corresponding":false},{"id":237537,"name":"Marc E. Rothenberg","orcid":"0000-0001-9790-6332","position":9,"is_corresponding":false},{"id":349883,"name":"Mark Rochman","orcid":"0000-0002-0818-927X","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T01:12:06.040073Z","pmid":"37490338","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}