{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:19:03Z","timestamp":1787505543627,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005834","name":"Parker B. Francis Family Foundation","doi-asserted-by":"publisher","award":["AWD-191474"],"award-info":[{"award-number":["AWD-191474"]}],"id":[{"id":"10.13039\/100005834","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005834","name":"Parker B. Francis Family Foundation","doi-asserted-by":"publisher","award":["W81XWH-16-PRMRP-FPA"],"award-info":[{"award-number":["W81XWH-16-PRMRP-FPA"]}],"id":[{"id":"10.13039\/100005834","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense award","doi-asserted-by":"publisher","award":["AWD-191474"],"award-info":[{"award-number":["AWD-191474"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense award","doi-asserted-by":"publisher","award":["W81XWH-16-PRMRP-FPA"],"award-info":[{"award-number":["W81XWH-16-PRMRP-FPA"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive disease of older adults characterized by fibrotic replacement of functional gas exchange units in the lung. The strongest risk factor for IPF is a genetic variantin the promoter region of the gel-forming mucin, MUC5B. To better understand how the MUC5B variant influences development of fibrosis, we used the NicheNet R package and leveraged publicly available single-cell RNA sequencing data to identify and evaluate how epithelia participating in gas exchange are influenced by ligands expressed in control, MUC5B variant, and fibrotic environments. We observed that loss of type-I alveolar epithelia (AECI) characterizes the single-cell RNA transcriptome in fibrotic lung and validated the pattern of AECI loss using single nuclear RNA sequencing. Examining AECI transcriptomes, we found enrichment of transcriptional signatures for IL6 and AREG, which we have previously shown to mediate aberrant epithelial fluidization in IPF and murine bleomycin models. Moreover, we found that the protease ADAM17, which is upstream of IL6 trans-signaling, was enriched in control MUC5B variant donors. We used immunofluorescence to validate a role for enhanced expression of ADAM17 among MUC5B variants, suggesting involvement in IPF pathogenesis and maintenance.<\/jats:p>","DOI":"10.3390\/cells11203319","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T20:43:50Z","timestamp":1666557830000},"page":"3319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dysregulated Cell\u2013Cell Communication Characterizes Pulmonary Fibrosis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4244-1870","authenticated-orcid":false,"given":"Jonathan S.","family":"Kurche","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Rocky Mountain Regional VA Medical Center, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian T.","family":"Stancil","sequence":"additional","affiliation":[{"name":"Program in Cellular Biology and Biophysics, Graduate School, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob E.","family":"Michalski","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana V.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Rocky Mountain Regional VA Medical Center, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/S2213-2600(14)70101-8","article-title":"Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: Incidence, prevalence, and survival, 2001\u20132011","volume":"2","author":"Raghu","year":"2014","journal-title":"Lancet Respir. 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