Induction of SREBP-1c mRNA by differentiation and LXR ligand in human keratinocytes

Ai Yokoyama, Makoto Makishima, Mihwa Choi, Yoshitake Cho, Shigeru Nishida, Yuichi Hashimoto, Tadashi Terui

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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-α (LXRα) and LXRΒ are nuclear receptors that are activated by oxysterols and regulate cholesterol and fatty acid metabolism. LXRs, predominantly LXRΒ, 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.

Original languageEnglish (US)
Pages (from-to)1395-1401
Number of pages7
JournalJournal of Investigative Dermatology
Issue number6
StatePublished - Jun 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


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