黑素细胞,位于表皮基底层,负责黑色素的产生,对于皮肤着色和防止紫外线辐射引起的损伤至关重要。黑色素的合成受到各种因素的复杂调节,包括Wnt信号通路,特别是由小眼症相关转录因子(MITF)介导。虽然MITF被认为是色素沉着的关键调节剂,其通过Wnt途径的调节仍然知之甚少。本研究调查了Sfrp5pepD的作用,Wnt信号通路的肽拮抗剂,调节黑色素生成及其对色素性疾病的潜在治疗意义。为了解决这个问题,我们研究了常用于化妆品或药物中的较小的肽。然而,关于与黑色素相关的信号调节或抑制黑色素产生相关的肽的报道非常稀缺。结果表明,Sfrp5pepD通过破坏Axin-1和β-catenin之间的相互作用有效抑制Wnt信号传导,从而阻碍下游黑色素生成过程。此外,Sfrp5pepD抑制MITF和β-catenin之间的相互作用,抑制其核易位并下调黑色素生成酶的表达,最终减少黑色素的产生。这些抑制作用在细胞培养模型中得到验证,表明了色素沉着过度疾病的潜在临床应用。总的来说,这项研究阐明了Wnt信号和黑素生成之间复杂的相互作用,强调Sfrp5pepD是一种有前途的色素性疾病治疗剂。Sfrp5pepD,分子量小于500Da,与SFRP不同,预计会穿透皮肤。这表明它们作为化妆品或经皮吸收剂的用途具有很强的潜力。有必要对其机制和临床意义进行进一步研究,以增强其在解决黑色素相关皮肤状况方面的有效性。
Melanocytes, located in the epidermis\' basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the
Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the
Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the
Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits
Wnt signaling by disrupting the interaction between Axin-1 and β-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and β-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between
Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.