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pubmed:abstractText |
The oxysterol nuclear receptors, LXR? (liver X receptor ?; NR1H3) and LXR? (NR1H2), coordinately regulate the expression of genes involved in lipid metabolism, anti-inflammation, and cholesterol transport. Previous studies have demonstrated that ligands of LXR? are important in the maintenance of the normal epidermal barrier function and keratinocyte differentiation. In this study, we examined whether LXR? and its ligands regulate lipid synthesis in HaCaT cells, a spontaneously transformed human keratinocyte cell line. When HaCaT cells were treated with the LXR? ligand TO901317, lipid droplets accumulated in the majority of cells, which were stained by Oil Red O. A luciferase reporter construct containing the LXR response element was activated about fourfold in HaCaT cells by TO901317 treatment, suggesting that LXR has a role in lipid synthesis in these cells. The expression of LXR? target genes, such as those encoding sterol regulatory binding protein and fatty acid synthase, were induced time dependently by TO901317, as measured by RT-PCR and western blotting. The expression of PPAR-?, -?, and -? which regulate lipid metabolism, was also increased by TO901317 treatment. In contrast, TO901317 reduced the lipopolysaccharide-induced expression of cyclooxygenase 2 and inducible nitric oxide synthase in HaCaT cells. These results indicate that LXR? activation leads to lipogenesis in keratinocytes, which may enhance the epidermal barrier function of the skin.
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pubmed:affiliation |
College of Pharmacy and Bio-MAX Institute, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Korea.
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