SENP2调控NF-κB/IL-6轴介导角质形成细胞异常对黑素细胞影响及机制研究

Vitiligo is an acquired depigmentation disorder. Although the melanocyte loss is the core of the pathogenesis of vitiligo, but cause white spot melanocyte loss the exact mechanism is unclear. Our previous research comfirmed that the basal keratinocytes stem cell of lesions proliferation increased, showed excessive differentiation and SUMO specific protease 2 high expression, suggested that keratinocytes of vitiligo lesions have protein SUMO modification abnormality. Group pilot study identified vitiligo lesion area keratinocyte excessive activation of formation,through the secretion of IL - 6 factors causing melanocyte apoptosis in vitro, suggested that keratinocyte-melanocyte cross - talk is abnormal; showed excessive differentiation and SUMO specific protease 2 high expression, suggesting that keratinocytes of vitiligo lesions have protein SUMO modification abnormality, and in vitro studies confirm SENP2 participate in horniness cells nf-kappa B positive feedback regulation of signaling pathways. 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, expounds the problem will make us from a new perspective to understand the melanocyte loss.

白癜风是获得性色素脱失性疾病。黑素细胞缺失是白癜风发病机制的核心，但导致白斑区黑素细胞缺失的确切机制尚不明确。课题组前期研究发现白癜风皮损区角质形成细胞过度活化，角质形成细胞通过分泌IL-6等细胞因子致使黑素细胞凋亡，提示皮损区角质形成细胞-黑素细胞间cross-talk存在异常；同时发现皮损区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，且体外研究证实SENP2参与角质形成细胞NF-κB信号通路的正反馈调节。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调控轴介导角质形成细胞-黑素细胞cross-talk的分子机制；构建SENP2表皮细胞特异性基因敲除小鼠模型，验证SENP2在白癜风发病中的作用。本研究将从一个全新的角度去理解黑素细胞缺失的分子机制，并可能为临床治疗提供新的生物靶点。

白癜风是获得性色素脱失性疾病。黑素细胞缺失是白癜风发病机制的核心，但导致白斑区黑素细胞缺失的确切机制尚不明确。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。课题组前期研究发现白癜风皮损区角质形成细胞过度活化，角质形成细胞通过分泌IL-6等细胞因子致使黑素细胞凋亡，提示皮损区角质形成细胞-黑素细胞间cross-talk存在异常；同时发现皮损区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，且体外研究证实SENP2参与角质形成细胞NF-κB信号通路的正反馈调节。本课题进一步验证白癜风患者皮损部位角质形成细胞存在SUMO化修饰异常，证实SUMO化修饰异常可影响角质形成细胞的细胞功能和趋化因子分泌异常，同时通过Hacat/MC共培养模型发现其能够影响黑素细胞功能相关基因表达从而影响黑素细胞生物学功能。以SENP-1及STAT1信号通路异常为切入点，深入研究发现SENP1可调控IFN-STAT1信号轴中关键蛋白的SUMO化修饰，从而影响角质形成细胞生物学活性和相关趋化因子分泌，进而造成角质形成细胞-黑素细胞cross-talk异常，致使黑素细胞生物学活性异常；同时筛选到IFN-STAT1信号轴中SUMO化调控的重要靶分子，为揭示白癜风的发病机制研究以及治疗提供新思路和靶点。

内容获取失败，请点击重试