Induction of SREBP-1c mRNA by Differentiation and LXR Ligand in Human Keratinocytes
Induction of SREBP-1c mRNA by Differentiation and LXR Ligand in Human Keratinocytes
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DOI：
10.1038/jid.2009.15
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发表时间：
2009-06-01
影响因子：
6.5
通讯作者：
Terui, Tadashi
中科院分区：
文献类型：
--
作者：
Yokoyama, Ai;Makishima, Makoto;Terui, Tadashi
表皮是脂质代谢的活跃部位，脂肪酸和胆固醇的合成是皮肤稳态所必需的。肝脏 X 受体-α (LXR α) 和 LXR β 是核受体，可被氧甾醇激活并调节胆固醇和脂肪酸代谢。 LXR（主要是 LXR β）已被证明参与角质形成细胞分化和表皮通透性屏障功能。尽管LXR通过诱导甾醇调节元件结合蛋白-1c (SREBP-1c)来调节肝脏脂肪生成，但LXR在表皮中诱导SREBP-1c的情况尚未研究。在这项研究中，我们报告说，SREBP-1c mRNA 在人角质形成细胞 HaCaT 细胞分化过程中增加，并且 LXR 激动剂有效诱导分化的 HaCaT 细胞中 LXR 靶基因的表达，包括 SREBP-1c 和 ATP 结合盒转运蛋白 A1。在恶性人角质形成细胞 A431 细胞和原代人角质形成细胞中也观察到 SREBP-1c 的分化相关和 LXR 增强表达。合成的 LXR 拮抗剂抑制 SREBP-1c 的汇合依赖性表达。因此，SREBP-1c 表达在角质形成细胞分化过程中增加，而 LXR 激活增强其表达。皮肤病学研究杂志 (2009) 129, 1395-1401； doi：10.1038/jid.2009.15； 2009 年 2 月 26 日在线发布
The epidermis is an active site of lipid metabolism, and the synthesis of fatty acids and cholesterol is required for cutaneous homeostasis. Liver X receptor-alpha (LXR alpha) and LXR beta are nuclear receptors that are activated by oxysterols and regulate cholesterol and fatty acid metabolism. LXRs, predominantly LXR beta, have been shown to be involved in keratinocyte differentiation and epidermal permeability barrier function. Although LXR regulates hepatic lipogenesis by inducing sterol-regulatory element-binding protein-1c (SREBP-1c), SREBP-1c induction by LXR in the epidermis has not been studied. In this study, we report that SREBP-1c mRNA increased during differentiation of human keratinocyte HaCaT cells and that LXR agonist effectively induced expression of LXR target genes, including SREBP-1c and ATP-binding cassette transporter A1, in differentiated HaCaT cells. Differentiation-associated and LXR-enhanced expression of SREBP-1c was also observed in malignant human keratinocyte A431 cells and primary human keratinocytes. A synthetic LXR antagonist inhibited confluency-dependent expression of SREBP-1c. Thus, SREBP-1c expression increases during keratinocyte differentiation, and LXR activation enhances its expression. Journal of Investigative Dermatology (2009) 129, 1395-1401; doi:10.1038/jid.2009.15; published online 26 February 2009