Activation of Transient Receptor Potential Vanilloid-3 Inhibits Human Hair Growth
Activation of Transient Receptor Potential Vanilloid-3 Inhibits Human Hair Growth
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DOI：
10.1038/jid.2011.122
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发表时间：
2011-08-01
影响因子：
6.5
通讯作者：
Biro, Tamas
中科院分区：
文献类型：
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作者：
Borbiro, Istvan;Lisztes, Erika;Biro, Tamas
在本研究中，我们旨在确定瞬时受体电位香草素-3 （TRPV3）离子通道在调节人类头发生长中的功能作用。利用人类器官培养的毛囊（HFs）和人类外根鞘（ORS）角质形成细胞的培养，我们首次提供了TRPV3激活抑制人类头发生长的证据。TRPV3的免疫反应性局限于人HF的上皮腔室，主要是ORS。在器官培养中，通过植物源性（如丁香酚，10- 1000 μ M）或人工合成（如2-氨基乙氧基二苯硼酸盐，1-300 μ M）激动剂激活TRPV3，导致毛干伸长的剂量依赖性抑制，增殖抑制，诱导细胞凋亡和HF过早消退（退化）。人ORS角质形成细胞也表达功能性TRPV3，其刺激诱导膜电流，升高细胞内钙浓度，抑制增殖，诱导凋亡。重要的是，这些对ORS角质形成细胞的影响都是由TRPV3介导的，因为小干扰rna介导的TRPV3沉默有效地消除了上述激动剂的细胞作用。这些发现共同支持TRPV3信号在人类头发生长控制中起重要作用的概念。因此，TRPV3和相关的细胞内信号机制可能是临床相关毛发生长障碍的药理操作的一个有希望的靶点。
In the current study, we aimed at identifying the functional role of transient receptor potential vanilloid-3 (TRPV3) ion channel in the regulation of human hair growth. Using human organ-cultured hair follicles (HFs) and cultures of human outer root sheath (ORS) keratinocytes, we provide the first evidence that activation of TRPV3 inhibits human hair growth. TRPV3 immunoreactivity was confined to epithelial compartments of the human HF, mainly to the ORS. In organ culture, TRPV3 activation by plant-derived (e. g., eugenol, 10-1,000 mu M) or synthetic (e. g., 2-aminoethoxydiphenyl borate, 1-300 mu M) agonists resulted in a dose-dependent inhibition of hair shaft elongation, suppression of proliferation, and induction of apoptosis and premature HF regression (catagen). Human ORS keratinocytes also expressed functional TRPV3, whose stimulation induced membrane currents, elevated intracellular calcium concentration, inhibited proliferation, and induced apoptosis. Of great importance, these effects on ORS keratinocytes were all mediated by TRPV3, as small interfering RNA-mediated silencing of TRPV3 effectively abrogated the cellular actions of the above agonists. These findings collectively support the concept that TRPV3 signaling is a significant player in human hair growth control. Therefore, TRPV3 and the related intracellular signaling mechanism might function as a promising target for pharmacological manipulations of clinically relevant hair growth disorders.