The vitamin D response element of the involucrin gene mediates its regulation by 1,25-dihydroxyvitamin D3

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:119

Article

Bikle, DD ; Ng, D ; Oda, Y ; Hanley, K ; Feingold, K ; Xie, ZJ

关键词: AP-1;    involucrin;    keratinocytes;    vitamin D receptor;    vitamin D response element;    PPAR alpha;    LXR;    delta P-1;    DR3;    PBS;   

DOI  :  10.1046/j.1523-1747.2002.19508.x

来源: Elsevier

【 摘 要 】

Involucrin is a major protein of the cornified envelope of keratinocytes that provides much of the structural integrity of skin. Its expression is stimulated by a number of agents including calcium and 1,25-dihydroxyvitamin D-3 that promote the differentiation process in keratinocytes. Within the distal regulatory region of the involucrin promoter lies an AP-1 site and an element homologous to other vitamin D response elements. In previous studies mutation of the AP-1 site was found to reduce basal activity and block calcium stimulation of the involucrin promoter, whereas the vitamin D response element was not critical for calcium regulation. In this study both elements proved to be important for 1,25-dihydroxyvitamin D-3 stimulation of the involucrin promoter. Mutation of the AP-1 site reduced basal activity and blocked 1,25-dihydroxyvitamin D-3 stimulation of the involucrin promoter. In contrast, mutation of the vitamin D response element did not reduce basal expression of the involucrin promoter or prevent calcium stimulation of involucrin gene expression, but blocked 1,25-dihydroxyvitamin D-3 stimulation. The vitamin D response element from the involucrin gene bound the vitamin D receptor and the retinoid X receptor, but not the retinoic acid receptor, in a specific manner. We conclude that the AP-1 site and the vitamin D response element in the involucrin promoter play important roles in mediating the action of 1,25-dihydroxyvitamin D-3 on involucrin expression, but the vitamin D response element provides specificity for the 1,25-dihydroxyvitamin D-3 response lacking at the AP-1 site.

【 授权许可】

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