Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin
Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin
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DOI：
10.1111/1523-1747.ep12276660
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发表时间：
1997-07-01
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
类维生素A通过两个核受体家族发挥其生物学作用，即视黄酸受体（RAR）和类维生素A X受体（RXR），它们属于类固醇/甲状腺激素核受体超家族。通过使用减法杂交方法，我们已经鉴定了cDNA序列TIG 2（他扎罗汀诱导的基因2），其表达通过用RAR β/γ选择性抗银屑病合成类维生素A他扎罗汀（AGN 190168/6-[2-（4，4-二甲基硫代苯并二氢吡喃-6-基）-乙炔基]烟酸乙酯）处理皮筏培养物而上调。通过北方印迹分析证实了维甲酸介导的TIG 2表达上调。测序后发现TIG 2是一个cDNA，其完整序列不在GenBank和EMBL数据库中。TIG 2 cDNA长830 bp，编码164个氨基酸的蛋白质产物。他扎罗汀在原代角质形成细胞和成纤维细胞培养物中既不表达也不诱导TIG 2。因此，只有当角质形成细胞和成纤维细胞形成组织样三维结构时，TIG 2才被他扎罗汀表达和诱导。我们进一步证明RAR特异性类维生素A增加TIG 2 mRNA水平。与此相反，无论是RXR特异性类维生素A还是1，25-二羟维生素D-3都不能增加TIG 2的水平。最后，我们证明了TIG 2在非皮损性银屑病皮肤中以高水平表达，但在银屑病皮损中以较低水平表达，并且在局部应用他扎罗汀后，其表达在银屑病皮损中上调。
Retinoids exert their biologic effects through two families of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which belong to the superfamily of steroid/thyroid hormone nuclear receptors. By using a subtraction hybridization approach, we have identified a cDNA sequence TIG2 (Tazarotene-induced gene 2), whose expression is up-regulated by the treatment of skin raft cultures by an RAR beta/gamma-selective anti-psoriatic synthetic retinoid tazarotene {AGN 190168/ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl] nicotinate). The retinoid-mediated up-regulation in the expression of TIG2 was confirmed by Northern blot analysis. Upon sequencing, TIG2 was found to be a cDNA whose complete sequence was not in the GenBank and EMBL data bases. The TIG2, cDNA is 830 bp long and encodes a putative protein product of 164 amino acids. TIG2 is neither expressed nor induced by tazarotene in primary keratinocyte and fibroblast cultures. Thus, TIG2 is expressed and induced by tazarotene only when keratinocytes and fibroblasts form a tissue-like 3-dimensional structure. We further demonstrate that RAR-specific retinoids increase TIG2 mRNA levels. In contrast, neither RXR-specific retinoids nor 1,25-dihydroxyvitamin D-3 increased TIG2 levels, Finally, we demonstrate that TIG2 is expressed at high levels in nonlesional psoriatic skin but at lower levels in the psoriatic lesion and that its expression is up-regulated in psoriatic lesions after topical application of tazarotene.