银屑病是一种常见的慢性炎症性皮肤疾病，角质形成细胞（KCs）的过度增殖在银屑病发病过程中起着重要作用。基于前期银屑病代谢组学的研究结果，我们发现银屑病患者体内血浆D-甘露糖水平降低与银屑病发病相关。进一步机制研究发现，D-甘露糖可以激活AMPK及后者下游重要分子TSC2，并初步明确了TSC2在银屑病发病过程中的作用。本项目科学假说：D-甘露糖通过AMPK调控TSC2/mTOR信号通路抑制KCs过度增殖及炎症因子释放对抗银屑病的发生发展。本项目拟从临床样本、动物模型及细胞生物学三个层面验证并深入研究D-甘露糖、新靶分子TSC2与银屑病发病之间的关系。以AMPK为桥梁，将D-甘露糖代谢所造成的细胞能量代谢变化与银屑病KCs过度增殖结合，阐明D-甘露糖通过调控TSC2/mTOR信号通路抑制KCs增殖对抗银屑病发生发展的作用机制。本项目有望探寻出银屑病治疗新方法和新靶分子。

Psoriasis is a common chronic inflammatory skin disease. The over- proliferation of keratinocytes (KCs) plays an important role in the pathogenesis of psoriasis. Based on the previous studies on the metabolomics of psoriasis, we found that the decrease of plasma level of D-mannose in psoriasis patients was related to the pathogenesis of psoriasis. Further studies have shown that D-Mannose can activate AMPK and TSC2 activity, and preliminarily confirmed the function of TSC2 in the pathogenesis of psoriasis. We proposed a novel hypothesis that D-mannose inhibit over-proliferation and inflammatory reaction of KCs by regulating the TSC2/mTOR signaling pathway through activates AMPK activity, and reduce exacerbation of psoriasis. We will study the function of D-mannose and TSC2 (new target molecule) in the pathogenesis of psoriasis from clinical samples, animal models and cell biology, and combine the changes in cellular energy metabolism caused by D-mannose with over-proliferation of KCs in psoriasis through AMPK, to determine the mechanism of D-mannose inhibit KCs proliferation by regulation of the TSC2/mTOR signaling pathway in the occurrence and development of psoriasis. This study is expected to discover the new methods and target molecule for the treatment of psoriasis.