Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin
Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin
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DOI：
10.1111/1523-1747.ep12340668
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发表时间：
1996-02-01
影响因子：
6.5
通讯作者：
Chandraratna, RAS
中科院分区：
文献类型：
--
作者：
Nagpal, S;Patel, S;Chandraratna, RAS
类视黄醇通过配体依赖性转录因子、视黄酸受体（RAR α、β 和 γ）和类视黄酸 X 受体（RXR α、β 和 γ）发挥作用，这些受体属于类固醇/甲状腺/维生素 D-3 核受体超家族。使用消减杂交方法，我们鉴定了他扎罗汀诱导基因 1 (TIG1) 的 cDNA 序列，该序列在皮筏培养物中通过 RAR β/γ 选择性视黄醇 AGN 190168（他扎罗汀/乙基 6-[2-(4,4-二甲基硫色满-6-基)-乙基]烟酸酯）高度上调，可有效治疗牛皮癣， Southern 和 Northern 分析证实了类视黄醇介导的 TIG1 表达上调。测序发现 TIG1 是一种新的 cDNA，编码 228 个氨基酸的蛋白质，其序列表明它是一种跨膜蛋白，具有小的 N 端胞内区域、单个跨膜疏水区域和含有糖基化信号的大 C 端胞外区域。我们证明，在由银屑病成纤维细胞和正常细胞制备的皮筏培养物中，TPG1 也被 AGN 190168 上调。角质形成细胞以及原代成纤维细胞和角质形成细胞培养物中。我们还表明，TIG1 被视黄酸受体上调，但不被类视黄醇 X 受体特异性合成类视黄醇上调。最后，我们证明，在银屑病临床治疗过程中，TIG1 是由 AGN 190168 在银屑病皮损中诱导的。
Retinoids exert their effect through ligand-dependent transcription factors, retinoic acid receptors (RAR alpha, beta, and gamma) and retinoid X receptor (RXR alpha, beta, and gamma), which belong to the superfamily of steroid/thyroid/vitamin D-3 nuclear receptors. Using a subtraction hybridization approach, we have identified a cDNA sequence, Tazarotene Induced Gene 1 (TIG1), which is highly upregulated in skin raft cultures by an RAR beta/gamma-selective retinoid AGN 190168 (tazarotene/ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethyl] nicotinate), which is effective in the treatment of psoriasis, The retinoid-mediated upregulation in the expression of TIG1 was confirmed by Southern and Northern analyses. Upon sequencing, TIG1 was found to be a novel cDNA which encodes a protein of 228 amino acids whose sequence suggests that it is a transmembrane protein with a small N-terminal intracellular region, a single membrane-spanning hydrophobic region, and a large C-terminal extracellular region containing a glycosylation signal, We demonstrate that TPG1 is also upregulated by AGN 190168 in skin raft cultures prepared from psoriatic fibroblasts and normal keratinocytes and in primary fibroblast and keratinocyte cultures. We also show that TIG1 is upregulated by retinoic acid receptor but not by retinoid X receptor-specific synthetic retinoids, Finally, we demonstrate that TIG1 is induced by AGN 190168 in psoriatic lesions during the course of clinical treatment of the disease.