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Keratin 4 upregulation by retinoic acid in vivo: a sensitive marker for retinoid bioactivity in human epidermis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Dermatology and Venereology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Dermatology and Venereology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Dermatology and Venereology)
2000 (English)In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 114, no 3, 487-493 p.Article in journal (Refereed) Published
Abstract [en]

Retinoids affect keratinocyte differentiation and modulate the expression of many epidermal proteins, among them cellular retinoic acid-binding protein II and the family of cytokeratins. The upregulation of the former protein is a well-known phenomenon, whereas the retinoid-induced regulation of epidermal keratin expression is more complex and only partially understood. We studied the effect of topical retinoids on the expression in healthy skin of cellular retinoic acid-binding protein II, tazarotene-induced genes 1 and 2, several epidermal keratins (K1, K2e, and K10), and two mucous keratins (K4 and K13) known to appear in epidermis under certain abnormal conditions. Reverse transcription-polymerase chain reaction experiments showed that the K4 expression was the one most overtly induced by 2 wk of open treatment with 0.05% of retinoic acid and tazarotene. Using real-time quantitative polymerase chain reaction (TaqMan) and normalization of the mRNA values to beta-actin, the increase in K4 was found to be 100-1000-fold. In comparison, the expression of K13 and cellular retinoic acid-binding protein II was increased 10-50-fold, the K1 and K10 mRNA levels remained unchanged, and the K2e level decreased by a factor of 100-1000. In parallel biopsies, immunohistochemistry showed no change in K1, K2e, or K10 staining, but a strong de novo appearance of K4 in the granular layer after retinoid treatment. In a separate study, occlusive application of 0.025% retinoic acid in four healthy subjects produced a maximal K4 mRNA signal after 48 h and strong K4 staining after 80 h. Finally, a dose-response study showed that the de novo appearance of K4 can be utilized as a sensitive test for retinoid bioactivity in epidermis in vivo.

Place, publisher, year, edition, pages
2000. Vol. 114, no 3, 487-493 p.
Keyword [en]
housekeeping genes, immunohistochemistry, quantitative real time polymerase chain reaction, tazarotene
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-54372DOI: 10.1046/j.1523-1747.2000.00901.xPubMedID: 10692107OAI: oai:DiVA.org:uu-54372DiVA: diva2:82281
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-04Bibliographically approved

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