SENP2介导的SUMO化修饰在白癜风移植中的作用及干预机制

项目名称： SENP2介导的SUMO化修饰在白癜风移植中的作用及干预机制

项目编号： No.81472887

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 许爱娥

作者单位： 安徽医科大学

项目金额： 80万元

中文摘要： 白癜风是获得性色素脱失性疾病，对患者造成毁容性损害，严重影响患者身心健康。我国发病率1%-2%，移植是治疗稳定期白癜风的有效手段。黑素细胞存活是移植成功的关键，目前影响黑素细胞存活的局部微环境免疫调控网络尚不明确。研究显示，白癜风患者存在角质形成细胞功能异常，局部微环境失衡，导致黑素细胞损伤。前期研究中白癜风皮损处基底层角质形成细胞干细胞过度活化，SUMO特异性蛋白酶2高表达，提示白癜风皮损处角质形成细胞存在蛋白SUMO化修饰异常。本课题以白癜风患者角质形成细胞中SENP2及NF-κB信号通路异常为切入点，深入研究 SENP2调控NF-κB/IL-6轴影响白癜风基底层角质形成细胞生物学活性，进而导致黑素细胞损伤的具体机制；利用SENP2表皮细胞特异性基因敲除小鼠模型，验证SENP2在白癜风发病以及黑素细胞移植中的作用，揭示白癜风的发病机制，为提高黑素细胞移植疗效提供重要的研究靶向因子。

中文关键词： 白癜风；黑素细胞移植；SUMO；化修饰；SUMO；特异性蛋白酶2

英文摘要： Vitiligo is an acquired depigmentation disorder, caused devastating damage to the patients, patients with serious impact on physical and mental health. The incidence rate of 1%-2% in our country, the melanocytes transplantation is an effective method for the treatment of stable vitiligo. Melanocyte effective survival is the key to successful transplantation, the effects of melanocyte survival microenvironment of immune regulatory network is not clear. Research shows that keratinocyte abnormalities in lesions can cause local micro environment imbalance, leading to the damage of the melanocytes. Confirm previous research, the basal keratinocytes stem cell of lesions proliferation increased, showed excessive differentiation and SUMO specific protease 2 high expression, suggesting that keratinocytes of vitiligo lesions have protein SUMO modification abnormality. This topic started with the abnormality of SENP2 and NF- κ B signal pathway in keratinocytes of patients with vitiligo, in-depth study the mechanism of SENP2 regulating the NF- κ B/IL-6 axis, which affects keratinocytes biological activity, leads to the damage of the melanocytes; SENP2 epithelial cell specific gene knockout mice model will be used to verify the effect of SENP2 in vitiligo development and melanocyte transplantation, to reveal the pathogenesis of vitiligo, research target important factor to improve the curative effect of transplantation of melanocytes.

英文关键词： vitiligo;melanocyte transplantation;SUMOylate;SENP2