TR3 is preferentially expressed by bulge epithelial stem cells in human hair follicles.
TR3 is preferentially expressed by bulge epithelial stem cells in human hair follicles.
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DOI：
10.1038/labinvest.2015.125
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发表时间：
2016-01
期刊：
影响因子：
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通讯作者：
Xu X
中科院分区：
文献类型：
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作者：
Xie L;Yang R;Liu S;Lyle S;Cotsarelis G;Xiang L;Zhang L;Li B;Wan M;Xu X
TR3是类固醇/甲状腺/维甲酸核受体超家族转录因子中的孤儿成员，在调节细胞生长和凋亡中起着关键作用。TR3在皮肤中的表达和功能尚未得到很好的研究。通过基因表达分析，我们发现与生长期相比，TR3在人的端原突起中显著富含。免疫组织化学染色证实TR3在人毛囊隆起区高表达，并与上皮干细胞标记物细胞角蛋白15(K15)共定位。为了研究TR3在雄激素对角质形成细胞的影响中的作用，我们用双氢睾酮(DHT)和睾酮(T)处理HaCaT角质形成细胞和原代人角质形成细胞。角质形成细胞对DHT和T.DHT的生长抑制呈剂量依赖性，DHT增加角质形成细胞TR3的表达，伴随着BAD的增加和Bcl-2表达的降低。SiRNA下调TR3的表达可阻断DHT对角质形成细胞增殖的抑制作用。我们的结果表明，TR3定位于人毛囊中的干细胞室。雄激素增加培养角质形成细胞中TR3的表达。我们的数据表明，TR3至少部分地介导了雄激素对角质形成细胞的抑制作用。
TR3 is an orphan member of the steroid/thyroid/retinoid nuclear receptor superfamily of transcription factors and it plays a pivotal role in regulating cell growth and apoptosis. The expression and function of TR3 in skin have not been well investigated. Using a cDNA expression assay, we discover that TR3 is significantly enriched in human telogen bulge compared with anagen bulb. Immunohistochemical staining confirms that TR3 is highly expressed in the bulge region of human hair follicles and it colocalizes with cytokeratin 15 (K15), an epithelial stem cell marker. To study the function of TR3 in the effect of androgens in keratinocytes, we treat HaCaT keratinocytes and primary human keratinocytes with dihydrotestosterone (DHT) and testosterone (T). The treated keratinocytes show a dose-dependent growth reduction to DHT and T. DHT increases the expression of TR3 in keratinocytes, associated with a concomitant increase of BAD and decrease of Bcl-2 expression. Knockdown TR3 expression by siRNA blocks the inhibitory effect of DHT on keratinocyte proliferation. Our results demonstrate that TR3 is localized to the stem cell compartment in the human hair follicles. Androgen increases TR3 expression in cultured keratinocytes. Our data suggest that TR3 mediates at least part of the inhibitory effect of androgens on keratinocytes.