Shorter Katie, Farjo Nilofer P, Picksley Steven M, Randall Valerie A
Department of Biomedical Sciences, University of Bradford, Bradford, BD7 1DP, UK.
FASEB J. 2008 Jun;22(6):1725-36. doi: 10.1096/fj.07-099424. Epub 2008 Feb 7.
Hair disorders cause psychological distress but are generally poorly controlled; more effective treatments are required. Despite the long-standing use of minoxidil for balding, its mechanism is unclear; suggestions include action on vasculature or follicle cells. Similar drugs also stimulate hair, implicating ATP-sensitive potassium (K(ATP)) channels. To investigate whether K(ATP) channels are present in human follicles, we used organ culture, molecular biological, and immunohistological approaches. Minoxidil and tolbutamide, a K(ATP) channel blocker, opposed each other's effects on the growing phase (anagen) of scalp follicles cultured in media with and without insulin. Reverse transcriptase-polymerase chain reaction identified K(ATP) channel component gene expression including regulatory sulfonylurea receptors (SUR) SUR1 and SUR2B but not SUR2A and pore-forming subunits (Kir) Kir6.1 and Kir6.2. When hair bulb tissues were examined separately, epithelial matrix expressed SUR1 and Kir6.2, whereas both dermal papilla and sheath exhibited SUR2B and Kir6.1. Immunohistochemistry demonstrated similar protein distributions. Thus, human follicles respond biologically to K(ATP) channel regulators in culture and express genes and proteins for two K(ATP) channels, Kir6.2/SUR1 and Kir6.1/SUR2B; minoxidil only stimulates SUR2 channels. These findings indicate that human follicular dermal papillae contain K(ATP) channels that can respond to minoxidil and that tolbutamide may suppress hair growth clinically; novel drugs designed specifically for these channels could treat hair disorders.
毛发疾病会导致心理困扰,但通常控制不佳,因此需要更有效的治疗方法。尽管米诺地尔长期用于治疗脱发,但其作用机制尚不清楚,有人认为它作用于血管系统或毛囊细胞。类似的药物也能刺激头发生长,这暗示了ATP敏感性钾(K(ATP))通道的作用。为了研究人毛囊中是否存在K(ATP)通道,我们采用了器官培养、分子生物学和免疫组织学方法。米诺地尔和K(ATP)通道阻滞剂甲苯磺丁脲在添加和不添加胰岛素的培养基中培养的头皮毛囊生长期(生长期)上具有相反的作用。逆转录聚合酶链反应确定了K(ATP)通道组成基因的表达,包括调节性磺脲类受体(SUR)SUR1和SUR2B,但不包括SUR2A以及成孔亚基(Kir)Kir6.1和Kir6.2。当分别检查毛球组织时,上皮基质表达SUR1和Kir6.2,而真皮乳头和毛囊鞘均表达SUR2B和Kir6.1。免疫组织化学显示了相似的蛋白质分布。因此,人毛囊在培养中对K(ATP)通道调节剂有生物学反应,并表达两种K(ATP)通道Kir6.2/SUR1和Kir6.1/SUR2B的基因和蛋白质;米诺地尔仅刺激SUR2通道。这些发现表明,人毛囊真皮乳头含有可对米诺地尔产生反应的K(ATP)通道,甲苯磺丁脲在临床上可能会抑制头发生长;专门针对这些通道设计的新型药物可能会治疗毛发疾病。