Retinoid induction of CRABP II mRNA in human dermal fibroblasts: Use as a retinoid bioassay

James T. Elder, Alex Kaplan, Matthew A. Cromie, Sewon Kang, John J. Voorhees

Research output: Contribution to journalArticle

Abstract

Cellular retinoic acid binding protein II (CRABP II) mRNA is selectively induced by all-trans retinoic acid in human skin and dermal fibroblasts. In order to determine whether this response can be used as a reliable measure of retinoid potency and activity, we treated human skin fibroblasts for 24 h with increasing concentrations of several natural and synthetic retinoids. CRABP II mRNA levels were measured by quantitative Northern blotting and compared, when possible, with those obtained after topical application of the same retinoids to human skin. All eight active retinoids tested induced a concentration-dependent CRABP II mRNA response in the fibroblast assay. In contrast, one known inactive retinoid (meta-carboxy TTNPB), differing from the active form only in the position of the carboxyl substituent, failed to evoke a response. The fibroblast and human skin bioassays agreed with respect to relative potency and response amplitude for three of the three retinoids tested, Retinoic acid was approximately 10-fold more potent than retinal in both assays, suggesting that oxidation to retinoic acid underlies the activity of retinol in fibroblasts as well as in intact skin, In support of this hypothesis, treatment with liarozole, an inhibitor of P450-mediated retinoic acid oxidative catabolism, significantly increased fibroblast CRABP II mRNA levels and potentiated the effects of retinol by 1.5-fold at concentrations at which it had no effect on its own, Taken together, these results identify the fibroblast CRABP II response as a reproducible measure of retinoid bioactivity with promise as a predictor of human skin responses and further suggest that metabolism is an important determinant of retinoid bioactivity in vivo.

Original languageEnglish (US)
Pages (from-to)517-521
Number of pages5
JournalJournal of Investigative Dermatology
Volume106
Issue number3
StatePublished - 1996
Externally publishedYes

Fingerprint

Bioassay
Retinoids
Fibroblasts
Biological Assay
Skin
Messenger RNA
Tretinoin
liarozole
Bioactivity
Vitamin A
Assays
cellular retinoic acid binding protein II
Metabolism
Human Activities
Northern Blotting
Oxidation

Keywords

  • Fibroblasts
  • Gene expression
  • Pharmacology
  • Retinoids

ASJC Scopus subject areas

  • Dermatology

Cite this

Retinoid induction of CRABP II mRNA in human dermal fibroblasts : Use as a retinoid bioassay. / Elder, James T.; Kaplan, Alex; Cromie, Matthew A.; Kang, Sewon; Voorhees, John J.

In: Journal of Investigative Dermatology, Vol. 106, No. 3, 1996, p. 517-521.

Research output: Contribution to journalArticle

Elder, James T. ; Kaplan, Alex ; Cromie, Matthew A. ; Kang, Sewon ; Voorhees, John J. / Retinoid induction of CRABP II mRNA in human dermal fibroblasts : Use as a retinoid bioassay. In: Journal of Investigative Dermatology. 1996 ; Vol. 106, No. 3. pp. 517-521.
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