{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:55:32Z","timestamp":1792468532641,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2001,12,1]],"date-time":"2001-12-01T00:00:00Z","timestamp":1007164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Retinoids play a critical role in the maintenance of the mucociliary phenotype of epithelial cells in the upper respiratory tract. To determine the role of retinoic acid receptors (RARs) in the regulation of epithelial differentiation, we tested the effect of the synthetic retinoids CD336, CD2019, and CD666, selective agonists for RAR \u03b1, RAR \u03b2, and RAR \u03b3, respectively, during differentiation of human nasal epithelial (HNE) cells in vitro. Using glutamylated tubulin and transglutaminase I (Tg I) as markers of ciliated cell and squamous cell differentiation, respectively, we showed that retinoic acid (RA) stimulated mucociliary differentiation and, in parallel, inhibited squamous cell differentiation. The agonists of the three RARs independently induced ciliogenesis and inhibited squamous cell differentiation by downregulating Tg I expression in a dose- and time-dependent manner. Antagonists specific for the three RARs abolished the effects of the corresponding agonists, demonstrating an RAR-specific mediated effect. Moreover, treatment of retinoid-deficient cultures with RAR agonists induced conversion of the squamous-like phenotype into a ciliated phenotype. In conclusion, all three RARs are potentially involved in the differentiating effects of RA in respiratory epithelial cells.<\/jats:p>","DOI":"10.1165\/ajrcmb.25.6.4549","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T21:40:45Z","timestamp":1365025245000},"page":"744-750","source":"Crossref","is-referenced-by-count":37,"title":["Effects of Retinoic Acid Receptor\u2013Selective Agonists on Human Nasal Epithelial Cell Differentiation"],"prefix":"10.1093","volume":"25","author":[{"given":"Karine","family":"Million","sequence":"first","affiliation":[{"name":"Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Paris; and Galderma, Research and Development, Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Tournier","sequence":"additional","affiliation":[{"name":"Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Paris; and Galderma, Research and Development, Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Houcine","sequence":"additional","affiliation":[{"name":"Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Paris; and Galderma, Research and Development, Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Ancian","sequence":"additional","affiliation":[{"name":"Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Paris; and Galderma, Research and Development, Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Reichert","sequence":"additional","affiliation":[{"name":"Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Paris; and Galderma, Research and Development, Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francelyne","family":"Marano","sequence":"additional","affiliation":[{"name":"Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Paris; and Galderma, Research and Development, Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,12,1]]},"reference":[{"key":"2026030700012658500_B1","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/0092-8674(95)90199-X","article-title":"The nuclear receptor superfamily: the second decade.","volume":"83","author":"Mangelsdorf","year":"1995","journal-title":"Cell"},{"key":"2026030700012658500_B2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/343177a0","article-title":"Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene.","volume":"343","author":"De Th\u00e9","year":"1990","journal-title":"Nature"},{"key":"2026030700012658500_B3","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1093\/jnci\/91.12.1059","article-title":"Expression of retinoid receptor genes and proteins in non-small-cell lung cancer.","volume":"91","author":"Picard","year":"1999","journal-title":"J. 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