{"doi":"10.1016/j.bbadis.2024.167572","title":"Integrated multiomic analysis identifies TRIP13 as a mediator of alveolar epithelial type II cell dysfunction in idiopathic pulmonary fibrosis","abstract":"Idiopathic pulmonary fibrosis (IPF) is a lethal progressive lung disease urgently needing new therapies. Current treatments only delay disease progression, leaving lung transplant as the sole remaining option. Recent studies support a model whereby IPF arises because alveolar epithelial type II (AT2) cells, which normally mediate distal lung regeneration, acquire airway and/or mesenchymal characteristics, preventing proper repair. Mechanisms driving this abnormal differentiation remain unclear. We performed integrated transcriptomic and epigenomic analysis of purified AT2 cells which revealed genome-wide alterations in IPF lungs. The most prominent epigenetic alteration was activation of an enhancer in thyroid receptor interactor 13 ( TRIP13 ), although TRIP13 was not the most significantly transcriptionally upregulated gene. TRIP13 is broadly implicated in epithelial-mesenchymal plasticity. In cultured human AT2 cells and lung slices, small molecule TRIP13 inhibitor DCZ0415 prevented acquisition of the mesenchymal gene signature characteristic of IPF, suggesting TRIP13 inhibition as a potential therapeutic approach to fibrotic disease. • Genome-wide transcriptomic and epigenomic alterations in IPF AT2 cells • TRIP13 expression elevated in IPF distal lung epithelium. • TRIP13 inhibition prevents epithelial-mesenchymal transition in human AT2 cells. • TRIP13 modulates STAT3 and WNT/β-catenin pathways in AT2 cells. • TRIP13 may be a novel therapeutic target in IPF.","journal":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease","year":2024,"id":469786,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1214411,"name":"Asres Berhan","orcid":"0000-0001-7406-0856","position":1,"is_corresponding":false},{"id":1303855,"name":"Eun Kyu Sung","orcid":null,"position":2,"is_corresponding":false},{"id":1303856,"name":"Juan R. Alvarez","orcid":null,"position":3,"is_corresponding":false},{"id":486699,"name":"Hongjun Wang","orcid":"0000-0001-7421-1917","position":4,"is_corresponding":false},{"id":505537,"name":"Yanbin Ji","orcid":null,"position":5,"is_corresponding":false},{"id":63565,"name":"Yixin Liu","orcid":"0000-0001-9043-3691","position":6,"is_corresponding":false},{"id":295030,"name":"Haoze Yu","orcid":"0000-0002-3831-2291","position":7,"is_corresponding":false},{"id":770115,"name":"Angela Meier","orcid":"0000-0002-6766-531X","position":8,"is_corresponding":false},{"id":875177,"name":"Kamyar Afshar","orcid":"0000-0002-7574-0738","position":9,"is_corresponding":false},{"id":704522,"name":"Eugene Golts","orcid":"0000-0002-6289-5773","position":10,"is_corresponding":false},{"id":391140,"name":"Grace Lin","orcid":"0000-0001-8018-5604","position":11,"is_corresponding":false},{"id":423512,"name":"Alessandra Castaldi","orcid":"0000-0002-6616-6519","position":12,"is_corresponding":false},{"id":468613,"name":"Ben A. Calvert","orcid":null,"position":13,"is_corresponding":false},{"id":467674,"name":"Amy L. Ryan","orcid":"0000-0003-1363-905X","position":14,"is_corresponding":false},{"id":356249,"name":"Beiyun Zhou","orcid":"0000-0002-9084-5933","position":15,"is_corresponding":false},{"id":423516,"name":"Ite A. Laird‐Offringa","orcid":"0000-0001-5729-6488","position":16,"is_corresponding":false},{"id":423517,"name":"Crystal N. Marconett","orcid":"0000-0002-8463-7126","position":17,"is_corresponding":false},{"id":239537,"name":"Zea Borok","orcid":"0000-0001-8673-8177","position":18,"is_corresponding":false},{"id":1303411,"name":"Laurence St. Pierre","orcid":"0000-0002-3019-186X","position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-19T02:05:32.241298Z","pmid":"39547519","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":[]}