SFRP5对黑色素细胞黑素合成的抑制及其机制探究

Inhibitory Effect of SFRP5 on Melanogenesis in Melanocytes and Its Mechanism

分泌型卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)是分泌卷曲相关蛋白家族的一员,在调节组织器官分化和发育中起着重要作用。但是SFRP5对黑色素细胞生物学功能的影响尚不清楚。该研究利用过表达SFRP5腺病毒(Ad-SFRP5)感染PIG1黑色素细胞,利用多巴氧化法、NaOH裂解法、qRT-PCR以及蛋白质免疫印迹等分析其对黑素合成相关指标的影响;并利用荧光素酶报告基因系统分析Ad-SFRP5对PIG1细胞中各信号通路活性的影响。研究结果表明,SFRP5在不影响PIG1细胞的增殖、凋亡以及细胞周期的情况下抑制PIG1细胞的酪氨酸酶活性和黑色素含量,并通过抑制Wnt/β-catenin信号通路下调小眼畸形相关转录因子(microphthalmia-associated transcription factor,MITF)及其靶蛋白的表达。该研究初步探讨了SFRP5通过调控Wnt信号通路对黑色素细胞黑素合成的抑制作用,为色素性皮肤病的治疗提供了新的治疗靶点。

Secreted frizzled-related protein 5 is a member of the family of secreted frizzled-related proteins,which plays an important role in regulating tissue differentiation and development.However,its effect on the biological function of melanocytes remains unclear.In this study,SFRP5 adenovirus (Ad-SFRP5) was used to infect PIG1 melanocytes,dopa oxidation,NaOH lysis,qRT-PCR,and Western blot were used to analyze the effects of SFRP5 on melanin synthesis-related indicators.The effect of Ad-SFRP5 on the activity of various signaling pathways in PIG1 cells was analyzed using the luciferase reporter gene system.The results showed that SFRP5 inhibited the tyrosinase activity and melanin synthesis of melanocytes without affecting the proliferation,apoptosis and cell cycle of PIG1 cells.Meanwhile,it downregulated the expression of microphthalmia-associated transcription factor (MITF) and its target protein by inhibiting the Wnt/β-catenin signaling pathway.This study initially explore the inhibitory effect of SFRP5 on melanin synthesis in melanocytes by regulating the Wnt signaling pathway,and provide a new therapeutic target for the treatment of pigmented skin diseases.