温敏型肝素泊洛沙姆-rhFGF9水凝胶通过Wnt信号通路促进毛囊周期转换及再生的机制研究

脱发疾病发病率高、对患者影响大，治疗仍有困难，筛选促进毛囊周期转换/再生的药物亟待研究。本团队合成了新型温敏型肝素泊洛沙姆-rhFGF9（HP-rhFGF9）水凝胶，初步发现其对毛囊具有调节作用，但具体机制不清。结合本团队前期关于FGFs及脱发类疾病发病机制研究，我们提出如下假说：FGF9结合FGFR后通过JAK/PI3K/AKT信号分子调节Wnt信号通路，调节毛囊干细胞增殖、分化、迁移等，进而调控毛囊周期转换/再生。本项目拟先在角质形成细胞/成纤维细胞研究HP-rhFGF9水凝胶如何通过JAK/PI3K/AKT调节Wnt信号通路；进而通过创伤修复诱导毛囊再生模型和tetO-Dkk1; K5rtTA转基因小鼠等，研究HP-rhFGF9水凝胶调节毛囊周期转换和再生的作用及机制。本项目能明确HP-rhFGF9水凝胶对毛囊生物学行为的调节机制和优势，为临床治疗脱发提供新药物。

Hair loss disorders are common clinical conditions and severely affect patients' quality of life. As a challenging problem for the treatment of hair loss disorders, more intensive studies are urgently needed to select medicines that effectively regulate hair follicle cycle transition and hair follicle regeneration. We recently constructed heparin-poloxamer recombinant human fibroblast growth factor 9 (HP-rhFGF9) gel. Our preliminary studies also confirmed that FGF9 could regulate hair follicles. However, it is still far away from the exact mechanisms of FGF9 in the regulations of hair follicles. Based on our previous studies of FGFs and alopecia, we hypothesized that FGF9/FGFR regulated Wnt signaling pathway via JAK/PI3K/AKT signaling molecules, and then regulated hair follicle cycle transition and regeneration. We plan to culture keratinocytes and fibroblasts, and study whether HP-rhFGF9 gel regulates Wnt signaling pathway via JAK/PI3K/AKT. Then we use HP-rhFGF9 intracutaneous injection mice model, wound induced hair neogenesis mice model, and tetO-Dkk1; K5rtTA mice model to study the regulations of hair follicles of HP-rhFGF9 gel. This project will help to illuminate the mechanisms and advantages of HP-rhFGF9 gel on the regulations of hair follicles, and select effective medicine for the treatment of hair loss disorders.