{"doi":"10.1016/j.isci.2023.106925","title":"Targeting the PRC2-dependent epigenetic program alleviates urinary tract infections","abstract":"Urinary tract infection (UTI) is a pervasive health problem worldwide. Patients with a history of UTIs suffer increased risk of recurrent infections, a major risk of antibiotic resistance. Here, we show that bladder infections induce expression of Ezh2 in bladder urothelial cells. Ezh2 is the methyltransferase of polycomb repressor complex 2 (PRC2)—a potent epigenetic regulator. Urothelium-specific inactivation of PRC2 results in reduced urine bacterial burden, muted inflammatory response, and decreased activity of the NF-κB signaling pathway. PRC2 inactivation also facilitates proper regeneration after urothelial damage from UTIs, by attenuating basal cell hyperplasia and increasing urothelial differentiation. In addition, treatment with Ezh2-specific small-molecule inhibitors improves outcomes of the chronic and severe bladder infections in mice. These findings collectively suggest that the PRC2-dependent epigenetic reprograming controls the amplitude of inflammation and severity of UTIs and that Ezh2 inhibitors may be a viable non-antibiotic strategy to manage chronic and severe UTIs.","journal":"iScience","year":2023,"id":378625,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"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":31605,"name":"Mingyi Zhao","orcid":"0000-0002-2884-0736","position":1,"is_corresponding":false},{"id":585367,"name":"Xinbing Sui","orcid":"0000-0001-7330-0467","position":2,"is_corresponding":false},{"id":586188,"name":"Zarine R. Balsara","orcid":null,"position":3,"is_corresponding":false},{"id":585368,"name":"Songhui Zhai","orcid":"0009-0007-5971-9123","position":4,"is_corresponding":false},{"id":218392,"name":"Michael Ahdoot","orcid":"0000-0002-5373-1283","position":5,"is_corresponding":false},{"id":830077,"name":"Yingsheng Zhang","orcid":"0000-0003-2520-3923","position":6,"is_corresponding":false},{"id":877983,"name":"Christa M. Lam","orcid":null,"position":7,"is_corresponding":false},{"id":585369,"name":"Ping Zhu","orcid":"0000-0002-4276-9593","position":8,"is_corresponding":false},{"id":585370,"name":"Xue Li","orcid":"0000-0002-3072-0573","position":9,"is_corresponding":false},{"id":585366,"name":"Chunming Guo","orcid":"0009-0007-6141-0037","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:16:48.594070Z","pmid":"37332606","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":[]}