{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:09:26Z","timestamp":1785431366604,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272212"],"award-info":[{"award-number":["82272212"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82272212"],"award-info":[{"award-number":["82272212"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) and Crohn\u2019s disease (CD) share overlapping immune and fibrotic processes, yet their convergent molecular mechanisms remain poorly defined. Here, we performed an integrative transcriptomic analysis of nine public datasets to identify shared transcriptional signatures across IPF and CD. The main discovery and validation analyses were based on bulk transcriptomic datasets and combined differential expression profiling, weighted gene co-expression network analysis, and machine-learning\u2013based feature prioritization. We identified 28 shared disease-associated module genes, from which three core genes\u2014ZNF395, EEF2K, and BAHD1\u2014were prioritized based on reproducibility and biological consistency. Functional enrichment analysis revealed their involvement in immune regulation, protein homeostasis, and stress-response pathways. Immune deconvolution and supportive single-cell RNA-sequencing further suggested associations between these genes and T-cell and myeloid cell populations, suggesting coordinated immune-fibrotic regulation. Experimental validation in a repetitive bleomycin challenge model and TGF-\u03b21-stimulated fibroblasts showed consistent downregulation of these genes during fibrotic remodeling, supporting their association with fibrosis-related transcriptional states. Collectively, our study identifies conserved immune\u2013fibrotic transcriptional programs shared across intestinal inflammation and pulmonary fibrosis, providing a hypothesis-generating molecular framework for understanding extraintestinal pulmonary involvement in Crohn\u2019s disease and prioritizing candidate genes for future mechanistic investigation.<\/jats:p>","DOI":"10.3390\/ijms27104428","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:40:31Z","timestamp":1779115231000},"page":"4428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Transcriptomic Analysis Identifies Shared Immune\u2013Fibrotic Transcriptional Programs Across Crohn\u2019s Disease and Idiopathic Pulmonary Fibrosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Renwei","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglu","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3749-9456","authenticated-orcid":false,"given":"Zhihao","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxuan","family":"Dan","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengling","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yige","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songping","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.matbio.2018.03.021","article-title":"Idiopathic pulmonary fibrosis: Epithelial-mesenchymal interactions and emerging therapeutic targets","volume":"71","author":"Hewlett","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1164\/rccm.201312-2221PP","article-title":"Revealing the Pathogenic and Aging-related Mechanisms of the Enigmatic Idiopathic Pulmonary Fibrosis. 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