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Here, we report the first intracellular proteomic analysis of CS exposure in fully differentiated primary human bronchial epithelial cells (phBECs). Following pathway enrichment analysis, we identified nuclear protein 1 (NUPR1) as a candidate regulator of epithelial stress responses. In contrast to the prediction by pathway enrichment analysis, NUPR1 activity was not altered by CS in vitro. Nevertheless, inhibition of its nuclear translocation using ZZW-115 revealed a cytoprotective and anti-apoptotic role in phBECs, as demonstrated by increased apoptosis and impaired epithelial integrity.\n                    <jats:italic>NUPR1<\/jats:italic>\n                    expression was markedly reduced in IPF whole lung tissue and bronchial epithelium. IPF-derived basal cells differentiated into an epithelium exhibiting fewer ciliated and more secretory cells which exhibited significantly higher sensitivity to NUPR1 inhibition. Our findings underscore cell type- and tissue-specific variation in NUPR1-dependent pathways. Collectively, this study positions NUPR1 as a context-dependent epithelial stress regulator whose loss may contribute to epithelial vulnerability in IPF.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-51510-1","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:05:58Z","timestamp":1778501158000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nuclear protein 1 is a cell death regulator in primary human airway epithelial cells and reduced in idiopathic pulmonary fibrosis"],"prefix":"10.1038","volume":"16","author":[{"given":"Marie","family":"Z\u00f6ller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Mastalerz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Dick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliane","family":"Merl-Pham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Hennen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai Rama Sridatta","family":"Prakki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashesh","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misako","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Klotz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Marchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronan","family":"LeGleut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurens J.","family":"De Sadeleer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wim A.","family":"Wuyts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart M.","family":"Vanaudenaerde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aicha","family":"Jeridi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antje","family":"Prasse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedikt","family":"J\u00e4ger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Santofimia-Casta\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mircea-Gabriel","family":"Stoleriu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Hilgendorff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie M.","family":"Hauck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali \u00d6.","family":"Yildirim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert","family":"Schiller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia A.","family":"Staab-Weijnitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"issue":"5","key":"51510_CR1","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.resinv.2020.04.002","volume":"58","author":"DS Glass","year":"2020","unstructured":"Glass, D. 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