Exosomes derived from dermal papilla cells mediate hair follicle stem cells proliferation through the Wnt3a/β-catenin signaling pathway

Both hair follicle stem cells (HFSC) and dermal papilla cells (DPC) are essential for hair follicle growth and proliferation. In this study, HFSCs and DPCs that made signature proteins like KRT14, KRT15, KRT19, α-SMA, and VIM were obtained. Cell co-culture systems between HFSCs and DPCs were used to measure the increased PCNA protein content in HFSCs. Additionally, exosomes from dermal papilla cells (DPC-Exos), the overexpression and silencing of Wnt3a could regulate the Wnt/β-catenin signaling pathway downstream genes. After collecting DPC-ExosOE-Wnt3a, the treatment of HFSC with DPC-ExosOE-Wnt3a showed that DPC-ExosOE-Wnt3a could upregulate the mRNA expression of downstream genes in the Wnt/β-catenin signaling pathway and that DPC-ExosOE-Wnt3a enhanced the proliferation of HFSCs while inhibiting their apoptosis. These findings suggest that DPC-Exos could regulate HFSC cell proliferation via the Wnt3a/β-catenin signaling pathway. This research offers novel concepts for the molecular breeding and efficient production of Angora rabbits, as well as for the treatment of human hair problems.

毛囊干细胞（hair follicle stem cells，HFSC）与真皮乳头细胞（dermal papilla cells，DPC）均为毛囊生长与增殖过程中不可或缺的关键细胞。本研究中，研究者成功获取了分别表达特征蛋白KRT14、KRT15、KRT19、α平滑肌肌动蛋白（α-SMA）及VIM的HFSCs与DPCs。通过构建HFSCs与DPCs的细胞共培养体系，检测发现HFSCs内的增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）蛋白含量显著升高。此外，真皮乳头细胞外泌体（DPC-Exos）相关实验显示，对Wnt3a进行过表达或沉默可调控Wnt/β-连环蛋白（β-catenin）信号通路的下游基因。在收集过表达Wnt3a的DPC外泌体（DPC-ExosOE-Wnt3a）后，将其用于处理HFSCs，结果表明DPC-ExosOE-Wnt3a可上调Wnt/β-连环蛋白信号通路下游基因的mRNA表达水平，同时可促进HFSCs的增殖并抑制其凋亡。上述研究结果证实，DPC外泌体可通过Wnt3a/β-连环蛋白信号通路调控毛囊干细胞的增殖。本研究为安哥拉兔（Angora rabbits）的分子育种与高效生产，以及人类毛发相关疾病的治疗提供了全新的研究思路。