Abstract：
Alopecia is a prevalent problem of cutaneous appendages and lacks effective therapy. Recently, researchers have been focusing on mesenchymal components of the hair follicle, i.e. dermal papilla cells, and we previously identified biglycan secreted by dermal papilla cells as the key factor responsible for hair follicle-inducing ability. In this research, we hypothesized biglycan played an important role in hair follicle cycle and regeneration through regulating the Wnt signalling pathway. To characterize the hair follicle cycle and the expression pattern of biglycan, we observed hair follicle morphology in C57BL/6 mice on Days 0, 3, 5, 12 and 18 post-depilation and found that biglycan is highly expressed at both mRNA and protein levels throughout anagen in HFs. To explore the role of biglycan during the phase transit process and regeneration, local injections were administered in C57BL/6 and nude mice. Results showed that local injection of biglycan in anagen HFs delayed catagen progression and involve activating the Wnt/β-catenin signalling pathway. Furthermore, local injection of biglycan induced HF regeneration and up-regulated expression of key Wnt factors in nude mice. In addition, cell analyses exhibited biglycan knockdown inactivated the Wnt signalling pathway in early-passage dermal papilla cell, whereas biglycan overexpression or incubation activated the Wnt signalling pathway in late-passage dermal papilla cells. These results indicate that biglycan plays a critical role in regulating HF cycle transit and regeneration in a paracrine and autocrine fashion by activating the Wnt/β-catenin signalling pathway and could be a potential treatment target for hair loss diseases.
摘要：
脱发是皮肤附件的普遍问题，缺乏有效的治疗方法。最近,研究人员一直专注于毛囊的间充质成分，即真皮乳头细胞，我们先前确定毛乳头细胞分泌的双糖链蛋白聚糖是毛囊诱导能力的关键因素。在这项研究中,我们假设biglycan通过调节Wnt信号通路在毛囊周期和再生中起重要作用。为了表征毛囊周期和双糖多糖的表达模式，我们在脱毛后第0、3、5、12和18天观察了C57BL/6小鼠的毛囊形态，并发现双糖链蛋白在HFs的整个生长期中以mRNA和蛋白质水平高度表达。探讨双糖链在相变过程和再生过程中的作用，对C57BL/6和裸鼠进行局部注射.结果表明，在生长期HFs中局部注射双糖链蛋白聚糖可延迟降生期进展，并涉及激活Wnt/β-catenin信号通路。此外，局部注射双糖多糖诱导裸鼠HF再生和关键Wnt因子表达上调。此外,细胞分析显示biglycan敲低了早期真皮乳头细胞中的Wnt信号通路，而biglycan过表达或孵育激活了晚期真皮乳头细胞中的Wnt信号通路。这些结果表明，双糖链蛋白通过激活Wnt/β-连环蛋白信号通路，在旁分泌和自分泌方式调节HF循环转运和再生中起关键作用，并且可能是脱发疾病的潜在治疗靶标。
