Abstract：
Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB-induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan-A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP-1 and TRP-2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p-GSK3β and β-catenin and the nuclear accumulation of β-catenin in B16F10 and Melan-A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis-related gene expression in melanocytes by regulating the Wnt/β-catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future.
摘要：
皮肤色素沉着主要是由黑色素的过度合成引起的;然而,目前尚无安全有效的治疗方法。这里,我们发现，皮肤冷冻能够改善UVB引起的豚鼠色素沉着，而不会引起明显的表皮损伤。我们还通过快速冷冻模拟细胞水平的冷冻刺激,并观察到冷冻处理<2.5分钟不能降低B16F10和Melan-A细胞的细胞活力或诱导细胞凋亡。严重的,冷冻处理后，两个细胞中的黑色素含量和酪氨酸酶活性大大降低。酪氨酸酶活性的急剧下降与MITF的下调有关，TYR,响应两个细胞的冷冻处理的TRP-1和TRP-2蛋白表达。此外，我们的结果首先表明，冷冻处理显着降低了β-GSK3β和β-catenin的水平以及β-catenin在B16F10和Melan-A细胞中的核积累。一起,这些数据表明，快速冷冻治疗可以通过调节Wnt/β-catenin信号通路来抑制黑素细胞中黑素生成相关基因的表达。黑色素产生的抑制最终有助于改善UVB诱导的皮肤色素沉着过度。因此,快速冷冻治疗可能是未来临床皮肤美白的新选择。
