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首页> 外文期刊>Journal of dermatological science >Minoxidil activates beta-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect.
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Minoxidil activates beta-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect.

机译：米诺地尔激活人真皮乳头细胞中的β-catenin途径：其生长期延长作用的可能解释。

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BACKGROUND: It is believed that the length of the actively growing phase of the anagen hair cycle mainly contributes to hair length. Recent studies showed that maintenance of beta-catenin activity in the dermal papilla cells (DPCs) enables hair follicles to keep actively growing. Topical minoxidil treatment promotes hair growth in men with androgenetic alopecia, suggesting that minoxidil may prolong the actively growing phase of the anagen hair cycle. OBJECTIVE: To investigate whether minoxidil prolongs the anagen hair cycle in mice and, if so, to investigate whether minoxidil activates beta-catenin pathway in human DPCs. METHODS: Dorsal skins of C57BL/6 mice were depilated to synchronize the hair cycle. After 10 days, 3% minoxidil were topically applied daily for 10 days. Sections of back skins were stained with hematoxylin and eosin. Hair follicles were graded and hair cycle score (HCS) was calculated. Cultured human DPCs were transiently transfected with the beta-catenin responsive TCF reporter plasmid (pTopflash) and corresponding negative control reporter (pFopflash) to assess the activity of beta-catenin signaling by minoxidil. Immunofluorescence staining and immunoblot were performed to examine the expression and localization of beta-catenin in the presence or absence of minoxidil. Phosphorylation of GSK3beta, PKA and PKB were also examined by immunoblot after minoxidil treatment. RT-PCR analysis and immunoblot were employed to investigate the expression of beta-catenin pathway targets in DPCs, such as Axin2, Lef-1, and EP2. RESULTS: Modest extension of anagen phase thereby delay of catagen progression was observed by application of minoxidil in mice. Minoxidil stimulated the transcriptional activity of pTopflash but not pFopflash. Nuclear accumulation of beta-catenin was also observed after minoxidil treatment. Immunoblot further showed that minoxidil treatment increases the phosphorylation of GSK3beta, PKA and PKB. Moreover, minoxidil induced Axin2, Lef-1, and EP2 expression. CONCLUSION: Our results strongly suggest that minoxidil extends the anagen phase by activating beta-catenin activity in the DPCs.
机译：背景：据信，毛发生长期活跃的生长期的长度主要影响头发的长度。最近的研究表明，维持皮肤乳头细胞（DPC）中的β-catenin活性可使毛囊保持活跃的生长。米诺地尔局部用药可促进雄激素性脱发男性的头发生长，表明米诺地尔可延长生长期毛发周期的活跃生长期。目的：研究米诺地尔是否延长小鼠的毛发生长周期，如果是，则调查米诺地尔是否激活人DPC中的β-catenin途径。方法：将C57BL / 6小鼠的背部皮肤脱毛以同步毛发周期。 10天后，每天局部使用3％米诺地尔10天。背部皮肤切片用苏木精和曙红染色。对毛囊进行分级并计算毛发周期得分（HCS）。用β-catenin反应性TCF报告质粒（pTopflash）和相应的阴性对照报告基因（pFopflash）瞬时转染培养的人DPC，以评估米诺地尔对β-catenin信号传导的活性。进行了免疫荧光染色和免疫印迹，以检查在存在或不存在米诺地尔的情况下β-catenin的表达和定位。米诺地尔处理后，还通过免疫印迹检查了GSK3beta，PKA和PKB的磷酸化。使用RT-PCR分析和免疫印迹来研究β连环蛋白途径靶标在DPC中的表达，如Axin2，Lef-1和EP2。结果：米诺地尔在小鼠中观察到生长期的适度扩展，从而延迟了生长期。米诺地尔刺激pTopflash的转录活性，但不刺激pFopflash。米诺地尔治疗后也观察到β-catenin的核积累。免疫印迹进一步表明，米诺地尔处理可增加GSK3beta，PKA和PKB的磷酸化。此外，米诺地尔诱导Axin2，Lef-1和EP2表达。结论：我们的结果强烈表明米诺地尔通过激活DPC中的β-catenin活性来延长生长期。

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