神经激肽1受体在皮肤色素合成中的作用及机制研究

Pigmentation disorder is a skin disease that seriously affects the patient’s appearance and mental health. Its etiology and pathogenesis has not yet been clarified. Wnt/β-catenin signaling pathway plays an important role in the synthesis of melanin. Our research group firstly demonstrated the existence of neurokinin 1 receptor (NK1R) in both of B16-F10 melanoma cells and primary human melanocytes. In addition, we found that neuropeptide substance P could inhibit the synthesis of melanin in the cells through upregulating the expression of NK1R. However, the role of NK1R and its mechanism in skin pigmentation has not yet been elucidated. Our preliminary experimental results indicated that promoting skin pigmentation of mice by NK1R antagonist is associated with boosting Wnt/β-catenin signaling pathway. On the basis of preliminary experiments, our project would establish animal and cell models to verify a scientific hypothesis: NK1R regulates Wnt/β-catenin signaling pathway, affects microphthalmia-associated transcription factor (MITF) expression, finally regulates the synthesis of melanin in the skin, which reveals the mechanism of NK1R in skin pigmentation, provides a new biological target for the treatment of pigmentation disorder and is of significant theoretical value and potential application.

色素障碍性皮肤病是严重影响患者容貌和心理健康的皮肤病，其病因及发病机理不明。Wnt/β-catenin信号通路在黑素合成中发挥重要作用。本项目组在前期工作中首次证实小鼠B16-F10黑素瘤细胞和人原代黑素细胞中存在神经激肽1受体（NK1R），并发现神经肽P物质可通过上调NK1R的表达来抑制细胞中黑素的合成，但NK1R在皮肤色素合成中的作用及其机制尚未阐明。申请人的预实验结果提示：NK1R拮抗剂对小鼠皮肤色素合成的促进作用与上调Wnt/β-catenin信号通路有关。在预实验的基础上，本项目拟从离体细胞与整体动物水平验证科学假说：NK1R可通过调控Wnt/β-catenin信号通路，影响小眼畸形相关转录因子（MITF）的表达，调节皮肤中黑素的合成，揭示NK1R在皮肤色素合成中的作用机制，为治疗色素障碍性皮肤病提供新的生物学靶点，具有重要的理论价值和潜在的应用前景。

色素障碍性皮肤病是严重影响患者容貌和心理健康的皮肤病，其病因及发病机理不明。Wnt/β-catenin信号通路在黑素合成中发挥重要作用。本项目组在前期工作中发现小鼠B16-F10黑素瘤细胞和人原代黑素细胞中存在神经激肽1受体（NK1R），并发现神经肽P物质可通过上调NK1R的表达来抑制细胞中黑素的合成，但NK1R在皮肤色素合成中的作用及其机制尚未阐明。本项目从离体细胞与整体动物水平，通过WB、TR-PCR、RNAi等实验发现NK1R可通过调控Wnt/β-catenin信号通路，影响小眼畸形相关转录因子（MITF）的表达，调节皮肤中黑素的合成，为治疗色素障碍性皮肤病提供新的生物学靶点，具有重要的理论价值和潜在的应用前景。