Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Hence, we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo. In this study, we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo. Compared with that in normal epidermal melanocytes (PIG1), the expression of SFRP5 was increased in vitiligo melanocytes (PIG3V). To investigate the effect of SFRP5 on melanin synthesis, PIG1 cells were infected with recombinant SFRP5 adenovirus (AdSFRP5), and PIG3V cells were infected with recombinant siSFRP5 adenovirus (AdsiSFRP5). The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor (MITF) and its target proteins via suppression of the Wnt/β-catenin signaling pathway. Accordingly, SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V cells. Moreover, SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor (TCF/LEF) in PIG1 cells. Furthermore, this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the β-catenin agonist, SKL2001. The inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse model. Hence, our results indicate that SFRP5 can inhibit melanogenesis in melanocytes. Additionally, our findings showed that SFRP5 plays a vital role in the development of vitiligo, and thus may serve as a potential therapeutic target for vitiligo.

分泌的卷曲相关蛋白 5 (SFRP5) 在调节许多组织和器官的发育中起着关键作用，然而，作为 Wnt 信号传导的抑制剂，SFRP5 在白斑病中的作用仍然未知。因此，我们推测 SFRP5 可能通过调节白斑病中的 Wnt 信号传导与黑素细胞中的黑色素生成有关。在本研究中，我们发现SFRP5在白癜风患者的皮损中过度表达。与正常表皮黑色素细胞（PIG1）相比，SFRP5在白斑黑色素细胞（PIG3V）中的表达增加。为了研究SFRP5对黑色素合成的影响，用重组SFRP5腺病毒（AdSFRP5）感染PIG1细胞，用重组siSFRP5腺病毒（AdsiSFRP5）感染PIG3V细胞。结果表明，SFRP5过表达通过抑制Wnt/β-catenin信号通路，下调小眼相关转录因子（MITF）及其靶蛋白，从而抑制PIG1细胞黑色素合成。因此，SFRP5 沉默增加了黑色素合成并激活了 PIG3V 细胞中的 Wnt 信号通路。此外，SFRP5 过表达还下调了 PIG1 细胞中 T 细胞因子/淋巴增强因子 (TCF/LEF) 的转录活性。此外，SFRP5 对黑色素合成的这种抑制作用被 β-连环蛋白激动剂 SKL2001 处理逆转。进一步证实了SFRP5对色素沉着的抑制作用 SFRP5 过表达还下调了 PIG1 细胞中 T 细胞因子/淋巴增强因子 (TCF/LEF) 的转录活性。此外，SFRP5 对黑色素合成的这种抑制作用被 β-连环蛋白激动剂 SKL2001 处理逆转。进一步证实了SFRP5对色素沉着的抑制作用 SFRP5 过表达还下调了 PIG1 细胞中 T 细胞因子/淋巴增强因子 (TCF/LEF) 的转录活性。此外，SFRP5 对黑色素合成的这种抑制作用被 β-连环蛋白激动剂 SKL2001 处理逆转。进一步证实了SFRP5对色素沉着的抑制作用 在体内 使用裸鼠模型。因此，我们的结果表明 SFRP5 可以抑制黑素细胞中的黑色素生成。此外，我们的研究结果表明，SFRP5 在白斑病的发展中起着至关重要的作用，因此可能作为白斑病的潜在治疗靶点。