■白癜风是一种自身免疫性疾病,其特征是皮肤色素沉着丧失,目前尚无有效的治疗方法。本研究旨在探讨SIRT7作为介导多种疾病进展的重要脱琥珀酶,及其在白癜风进展中的作用机制。
■在本研究中利用正常人黑素细胞(NHM)PIG1和白癜风人黑素细胞(VHM)PIG3V。通过检测酪氨酸酶活性研究了沉默蛋白7(SIRT7)和Ezrin(EZR)对黑色素合成的作用,黑色素含量,α-MSH电平,和黑色素相关标志物的蛋白质水平。EZR的功能是通过救援实验确定的,虽然通过生物信息学分析研究了潜在的机制,免疫共沉淀(co-IP),免疫沉淀(IP),和蛋白质印迹技术。
■结果表明,只有SIRT7在白癜风人黑素细胞中高表达,其中敲低SIRT7转化为黑素细胞中黑色素合成增加。机械上,SIRT7敲低促进了EZR在Lys(K)60位点的琥珀酰化。此外,过表达EZR诱导黑素细胞中更高的黑色素合成,而其敲除通过抑制SIRT7敲除诱导的黑色素合成而发挥相反的作用。
■SIRT7通过抑制EZR的琥珀酰化而抑制黑素细胞中的黑色素合成。这些发现旨在为白癜风的治疗提供新的理论基础。
UNASSIGNED: Vitiligo is an autoimmune disease characterized by loss of skin pigmentation and currently has no effective treatment. This study aimed to investigate the function of SIRT7, being an important desuccinylase mediating multiple disease progression, and its mechanism in vitiligo progression.
UNASSIGNED: Normal human melanocytes (NHM) PIG1 and vitiligo human melanocytes (VHM) PIG3V were utilized in this research. The role of sirtuin 7 (SIRT7) and Ezrin (EZR) on melanin synthesis was investigated by detecting tyrosinase activity, melanin content, α-MSH levels, and the protein levels of melanin-related markers. The function of EZR was identified via rescue experiments, while the underlying mechanism was investigated via bioinformatic analysis, co-immunoprecipitation (co-IP), immunoprecipitation (IP), and Western blot techniques.
UNASSIGNED: Results showed that only SIRT7 was highly expressed in vitiligo human melanocytes, where knockingdown SIRT7 translated into increased melanin synthesis in melanocytes. Mechanistically, SIRT7 knockdown promoted the
succinylation of EZR at the Lys (K)60 site. Moreover, overexpressing EZR induced higher melanin synthesis in melanocytes, while its knocking down exerted the opposite effect by inhibiting SIRT7 knockdown-induced melanin synthesis.
UNASSIGNED: SIRT7 inhibited melanin synthesis in melanocytes by suppressing the
succinylation of EZR. These findings are envisaged to provide a novel theoretical basis for vitiligo treatment.