Characterization of liver X receptor expression and function in human skin and the pilosebaceous unit.
The nuclear receptors liver X receptor alpha (LXRalpha) and liver X-receptor beta (LXRbeta) have a well documented role in cholesterol homeostasis and lipid metabolism within tissues and cells including the liver, small intestine and macrophages. In keratinocytes, LXRs have been shown to up-regulate differentiation in vitro via increased transcription of proteins of the AP1 complex and to down-regulate proliferation in vivo. In this study, we provide a detailed description of the location and possible role of LXRs within human skin and its associated glands and appendages. Using RT-PCR, Western blotting and immunohistochemistry, we have demonstrated expression of LXRalpha and LXRbeta mRNA and proteins in whole human skin as well as within a range of primary and immortalized human cell lines derived from human skin, hair follicle and sebaceous glands. Furthermore, we have shown that synthetic LXR specific agonists GW683965 and TO901317 significantly inhibit cell proliferation in primary epidermal keratinocytes, immortalized N/TERT keratinocytes and the immortalized SZ95 sebocyte line, and significantly increase lipogenesis in SZ95 sebocytes. In addition, we showed that the synthetic agonist TO901317 significantly reduced hair growth, in vitro.
Russell
Louise E
LE
Centre for Cutaneous Research and Centre for Endocrinology, Bart's and The London Queen Mary's School of Medicine and Dentistry, Queen Mary College, University of London, London, UK.
Harrison
Wesley J
WJ
Bahta
Adiam W
AW
Zouboulis
Christos C
CC
Burrin
Jacky M
JM
Philpott
Michael P
MP
D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006197:Hair / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010648:Phenylacetates / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012627:Sebaceous Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013545:Sweat Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D010648:Phenylacetates; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides