Keratin 4 upregulation by retinoic acid in vivo: a sensitive marker for retinoid bioactivity in human epidermis
2000 (English)In: Journal of Investigative Dermatology, ISSN 0022-202X, Vol. 114, no 3, 487-493 p.Article in journal (Refereed) Published
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.
housekeeping genes, immunohistochemistry, quantitative real time polymerase chain reaction, tazarotene
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-54372DOI: 10.1046/j.1523-1747.2000.00901.xPubMedID: 10692107OAI: oai:DiVA.org:uu-54372DiVA: diva2:82281