Dermal papilla cell-secreted biglycan regulates hair follicle phase transit and regeneration by activating Wnt/β-catenin.
Dermal papilla cell-secreted biglycan regulates hair follicle phase transit and regeneration by activating Wnt/β-catenin.
复制标题
DOI：
10.1111/exd.14969
复制
发表时间：
2023-11
影响因子：
3.6
通讯作者：
Ningxia Zhu;Junping Yan;Weifan Gu;Qilin Yang;En Lin;Siyue Lu;Bozhi Cai;Bin Xia;Xin Liu;Changmin Lin
中科院分区：
文献类型：
--
作者：
Ningxia Zhu;Junping Yan;Weifan Gu;Qilin Yang;En Lin;Siyue Lu;Bozhi Cai;Bin Xia;Xin Liu;Changmin Lin
脱发是一个普遍的问题，皮肤附件，缺乏有效的治疗。最近，研究人员一直专注于毛囊的间充质成分，即毛乳头细胞，我们以前确定了毛乳头细胞分泌的双糖蛋白聚糖是毛囊诱导能力的关键因素。在本研究中，我们假设biglycan通过调节Wnt信号通路在毛囊周期和再生中发挥重要作用。为了表征毛囊周期和biglycan的表达模式，我们在脱毛后第0、3、5、12和18天观察了C57 BL/6小鼠的毛囊形态，发现biglycan在毛发生长期的整个毛发生长期在mRNA和蛋白水平上都高度表达。为了探索双糖蛋白聚糖在相转变过程和再生过程中的作用，在C57 BL/6和裸鼠中局部注射。结果显示，在生长期HF中局部注射双糖链蛋白聚糖延迟了退行期进展，并涉及激活Wnt/β-连环蛋白信号传导通路。此外，局部注射双糖链蛋白聚糖诱导裸鼠HF再生和关键Wnt因子的上调表达。此外，细胞分析显示双糖蛋白聚糖敲低使早期传代毛乳头细胞中的Wnt信号传导途径失活，而双糖蛋白聚糖过表达或孵育使晚期传代毛乳头细胞中的Wnt信号传导途径活化。这些结果表明，双糖链蛋白聚糖通过激活Wnt/β-连环蛋白信号通路，以旁分泌和自分泌方式在调节HF循环转运和再生中发挥关键作用，并可能成为脱发疾病的潜在治疗靶点。
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.