文章基本信息

标题：Regulation of ABCA1 expression in human keratinocytes and murine epidermis
本地全文：下载
作者：Jiang, Yan J. ; Lu, Biao ; Kim, Peggy 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2006
卷号：47
期号：10
页码：2248-2258
DOI：10.1194/jlr.M600163-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Keratinocytes require abundant cholesterol for cutaneous permeabilitybarrier function; hence, the regulation of cholesterol homeostasisis of great importance. ABCA1 is a membrane transporter responsiblefor cholesterol efflux and plays a pivotal role in regulatingcellular cholesterol levels. We demonstrate that ABCA1 is expressedin cultured human keratinocytes (CHKs) and murine epidermis.Liver X receptor (LXR) activation markedly stimulates ABCA1mRNA and protein levels in CHKs and mouse epidermis. In additionto LXR, activators of peroxisome proliferator-activated receptor(PPAR) ${alpha}$ , PPARß/ ${delta}$ , and retinoid X receptor (RXR), butneither PPAR ${gamma}$ nor retinoic acid receptor, also increase ABCA1expression in CHKs. Increases in cholesterol supply inducedby LDL or mevalonate stimulate ABCA1 expression, whereas inhibitingcholesterol synthesis with statins or cholesterol sulfate decreasesABCA1 expression in CHKs. After acute permeability barrier disruptionby either tape-stripping or acetone treatment, ABCA1 expressiondeclines, and this attenuates cellular cholesterol efflux, makingmore cholesterol available for regeneration of the barrier.In addition, during fetal epidermal development, ABCA1 expressiondecreases at days 18–22 of gestation (term = 22 days),leaving more cholesterol available during the critical periodof barrier formation. Together, our results show that ABCA1is expressed in keratinocytes, where it is negatively regulatedby a decrease in cellular cholesterol levels or altered permeabilitybarrier requirements and positively regulated by activatorsof LXR, PPARs, and RXR or increases in cellular cholesterollevels. Supplementary key words ATP binding cassette transporter 1 • liver X receptor • peroxisome proliferator-activated receptor ${alpha}$ • peroxisome proliferator-activated receptor ${delta}$ • peroxisome proliferator-activated receptor ${gamma}$ • cultured human keratinocyte Abbreviations: ATRA, all-trans-retinoic acid; 8-Br-cAMP, 8-bromoadenosine-3',5'-cyclic monophosphate; CHK, cultured human keratinocyte; 9-cis-RA, 9-cis-retinoic acid; CS, cholesterol sulfate; LXR, liver X receptor; 25(OH), 25-hydroxycholesterol; PPAR, peroxisome proliferator-activated receptor; 22R, 22(R)-hydroxycholesterol; RXR, retinoid X receptor; TO, TO901317