{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:10:39Z","timestamp":1780758639275,"version":"3.54.1"},"reference-count":58,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["CIPROM\/2021\/051"],"award-info":[{"award-number":["CIPROM\/2021\/051"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin A deficiency (VAD) induced TGF-\u03b2 hyperactivation and reduced expression of cell adhesion proteins in the lung, suggesting that the disruption of retinoic acid (RA) signaling leads to epithelial\u2013mesenchymal transition (EMT). To elucidate the role of lung vitamin A status in EMT, several EMT markers and the expression of the proprotein convertase furin, which activates TGF-\u03b2, were analyzed in two experimental models. Our in vivo model included control rats, VAD rats, and both control rats and VAD rats, treated with RA. For the in vitro studies, human bronchoalveolar epithelial cells treated with RA were used. Our data show that EMT and furin are induced in VAD rats. Furthermore, furin expression continues to increase much more markedly after treatment of VAD rats with RA. In control rats and cell lines, an acute RA treatment induced a significant increase in furin expression, concomitant with changes in EMT markers. A ChIP assay demonstrated that RA directly regulates furin transcription. These results emphasize the importance of maintaining vitamin A levels within the physiological range since both levels below and above this range can cause adverse effects that, paradoxically, could be similar. The role of furin in EMT is discussed.<\/jats:p>","DOI":"10.3390\/nu16081177","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T11:53:53Z","timestamp":1713182033000},"page":"1177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vitamin A Status Modulates Epithelial Mesenchymal Transition in the Lung: The Role of Furin"],"prefix":"10.3390","volume":"16","author":[{"given":"M. Teresa","family":"Cabezuelo","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Valencia, 46010 Valencia, Spain"},{"name":"Centro Salud Safranar, Hospital Universitario Doctor Peset, 46017 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology-IIS INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7437-4772","authenticated-orcid":false,"given":"Elena","family":"Ortiz-Zapater","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology-IIS INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8367-653X","authenticated-orcid":false,"given":"Gerardo","family":"L\u00f3pez-Rodas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology-IIS INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Pilar","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Microscopy Unit IIS La Fe Valencia, 46009 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Timoneda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology-IIS INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan R.","family":"Vi\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology-IIS INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Zaragoz\u00e1","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Embryology-IIS INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Barber","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology-IIS INCLIVA, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000258434","article-title":"Vitamin A in nature","volume":"103","author":"McLaren","year":"2012","journal-title":"World Rev. 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