Retinoic acid receptors and binding proteins in human skin.
Nuclear retinoic acid receptors (RAR) are likely to mediate many of the pleiotypic cutaneous actions of retinoids by acting as ligand-dependent enhancer factors. The presence of nuclear RAR in skin was confirmed by identification of a 45-kDa nuclear RA binding activity by fast protein liquid chromatography (FPLC). Analysis of RNA extracted from skin specimens demonstrated expression of RAR-alpha and RAR-gamma transcripts, as well as expression of the homologous low-affinity receptor, RXR-alpha. Both isoforms of RAR-gamma RAR-gamma 1 and RAR-gamma 2 were detectable, with RAR-gamma 1 being the more strongly expressed. FPLC analysis also demonstrated a 15-kDa peak of specific RA binding activity, consistent with the presence of cellular retinoic acid binding protein (CRABP). Of the two known forms of CRABP, CRABP-II was much more strongly expressed than CRABP-I at the level of steady-state mRNA. CRABP-II was also expressed in keratinocytes and fibroblasts in vitro. CRABP-II was up-regulated by agents that induce keratinocyte differentiation, and inhibited by prolonged exposure to high concentrations of RA. In contrast, CRABP-II was consistently induced by RA in dermal, but not in lung fibroblasts. CRABP-I was expressed at low to undetectable levels under all these conditions. The presence of tissue-specific and differentiation-related regulation of CRABP-II suggests that it may be an important regulator of RA action in human skin.
Elder
J T
JT
Department of Dermatology, University of Michigan, Ann Arbor 48109-0672.
Aström
A
A
Pettersson
U
U
Tavakkol
A
A
Krust
A
A
Kastner
P
P
Chambon
P
P
Voorhees
J J
JJ
D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D007536:Isomerism; D015603:Keratinocytes / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid; D012867:Skin / Q000737:chemistry* / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology
D002352:Carrier Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014212:Tretinoin