Retinoic acid induces expression of early growth response gene-1 (Egr-1) in human skin in vivo and in cultured skin fibroblasts.
The early growth response gene, Egr-1 (NGFI-A, krox 24, zif 268, TIS 8), is a member of a family of genes with suggested importance in the regulation of cell growth and differentiation. Retinoic acid has been shown to markedly induce Egr-1 gene expression in mouse embryonal carcinoma cells and rat preosteoblastic cells. In this study we demonstrate that treatment of cultured human skin fibroblasts with retinoic acid results in a rapid transient four-fold induction of Egr-1 transcripts, being maximum at 60 min and returning to a basal level by 120 min. However, treatment of cultured human keratinocytes with retinoic acid did not significantly induce Egr-1 transcripts. Expression of Egr-1 message in keratinocytes was observed to be induced by fetal bovine serum and tetra-decanoyl phorbol acetate, whereas calcium, 1,25-dihydroxyvitamin D3, and cyclic adenosine monophosphate caused little or no induction. Topical application of 0.1% retinoic acid cream in vivo resulted in a two- to threefold induction of Egr-1 transcripts following treatment for 24 and 48 h, returning to nearly basal levels by 96 h. Taken together, these data are consistent with the possibility that Egr-1 is a proximal component of an intracellular molecular cascade that may give rise to alterations in cell phenotype in response to retinoic acid.
Larsen
F G
FG
Department of Dermatology, University of Michigan, Ann Arbor.
Voorhees
J J
JJ
Aström
A
A
D015152:Blotting, Northern; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D017874:Immediate-Early Proteins; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena; D014157:Transcription Factors / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014212:Tretinoin