血管生成素活化mTOR信号通路诱导毛囊周期性再生的作用及机制研究

The abnormality of hair follicle regeneration can result in hair loss. Hair follicle stem cells activation and dermal papilla cells proliferation are very important in the hair follicle regeneration. The mTOR signaling pathway is involved in a variety of stem cell activation and cell proliferation. Our previous study found that angiogenin can induce the hair follicle regeneration. Therefore, mTOR may be involved in the process of angiogenin-induced hair follicle regeneration. To this end, we put forward the hypothesis that the binding of angiogenin and its receptor can activate mTOR signaling pathway and induce the hair follicle regeneration by activating hair follicle stem cells and promoting dermal papilla cells proliferation. To test this hypothesis, we apply the gene overexpression and gene knockout technologies from three levels including C57BL/6 mice, cultured hair follicles and hair follicle cells, and use western blot, immunofluorescence staining methods to observe the expression of key molecules and signaling pathway activation. This study has important significance to classify the hair follicle stem cells activation and dermal papilla cells proliferation in the mTOR signaling pathway activation in angiogenin-induced hair follicle regeneration, and will provide new ideas and theoretical basis for the clinical treatment of alopecia.

毛囊周期性再生出现紊乱或异常可导致脱发的发生，毛囊干细胞的活化和毛乳头细胞的增殖在毛囊周期性再生中发挥重要作用，mTOR信号通路参与多种干细胞的活化与细胞的增殖过程，本课题组的前期研究发现血管生成素能够诱导毛囊周期性再生，因而mTOR信号通路可能参与血管生成素诱导毛囊周期性再生的过程。为此，我们提出假说：血管生成素与其受体结合，激活mTOR信号通路后，通过活化毛囊干细胞与促进毛乳头细胞增殖而诱导毛囊周期性再生。为验证该假说，我们从C57BL/6小鼠、培养的毛囊器官及毛囊细胞三个水平，利用基因过表达和基因敲除技术，通过western blot、免疫荧光染色、细胞增殖测定等手段，观察mTOR信号通路关键分子的表达与激活情况，在体内和体外分析探讨mTOR信号通路在血管生成素诱导毛囊周期性再生中可能的作用机制，为临床治疗脱发性疾病提供新的思路和理论依据。

毛囊周期性再生发生紊乱或异常可导致脱发的发生，毛囊干细胞的活化和毛乳头细胞的增殖在毛囊周期性再生中发挥重要作用，mTOR信号通路参与多种干细胞的活化与细胞的增殖过程。既往的研究发现：血管生成素不仅具有促进毛乳头细胞增殖和促进毛发生长的作用，还能够诱导毛囊周期性再生。本课题通过上调小鼠皮肤、毛囊及毛囊细胞中血管生成素的表达，研究血管生成素对毛囊周期的影响及毛囊细胞增殖活化的作用，并探讨其可能的作用机制。结果发现：血管生成素在小鼠不同毛发周期中的表达与分布具有毛发周期依赖性的特征，血管生成素能够通过活化mTOR信号通路促进小鼠毛囊外毛根鞘细胞和人毛乳头细胞的增殖，小鼠皮肤局部过表达血管生成素可通过活化mTOR信号通路诱导毛囊的周期性再生，促进毛囊提前由休止期进入生长期。本研究阐明了血管生成素能够通过活化毛囊细胞的mTOR信号通路诱导毛囊的周期性再生，可为临床治疗脱发性疾病提供新的思路和理论依据。