Activation of LXR alpha Induces Lipogenesis in HaCaT Cells

作者：Hong Il; Rho Ho Sik; Kim Duck Hee; Lee Mi Ock^*

来源：Archives of Pharmacal Research, 2010, 33(9): 1443-1449.

DOI：10.1007/s12272-010-0919-5

• LXR
• HaCaT
• Lipid metabolism
• Inflammation

The oxysterol nuclear receptors, LXR alpha (liver X receptor alpha; NR1H3) and LXR beta (NR1H2), coordinately regulate the expression of genes involved in lipid metabolism, anti-inflammation, and cholesterol transport. Previous studies have demonstrated that ligands of LXR alpha are important in the maintenance of the normal epidermal barrier function and keratinocyte differentiation. In this study, we examined whether LXRa and its ligands regulate lipid synthesis in HaCaT cells, a spontaneously transformed human keratinocyte cell line. When HaCaT cells were treated with the LXRa 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 alpha 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-alpha, -beta, and -gamma 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 alpha activation leads to lipogenesis in keratinocytes, which may enhance the epidermal barrier function of the skin.

• 出版日期2010-9