PDF(Pubmed)
Abstract：
Fibroblast growth factor 5 (FGF5) plays key roles in promoting the transition from the anagen to catagen during the hair follicle cycle. The sheep serves as an excellent model for studying hair growth and is frequently utilized in various research processes related to human skin diseases. We used the CRISPR/Cas9 system to generate four FGF5-edited Dorper sheep and only low levels of FGF5 were detected in the edited sheep. The density of fine wool in GE sheep was markedly increased, and the proportion of fine wool with a diameter of 14.4-20.0 μm was significantly higher. The proliferation signal in the skin of gene-edited (GE) sheep was stronger than in wild-type (WT) sheep. FGF5 editing decreased cortisol concentration in the skin, further activated the activity of antioxidant enzymes such as Glutathione peroxidase (GSH-Px), and regulated the expression of Wnt signaling pathways containing Wnt agonists (Rspondins, Rspos) and antagonists (Notum) in hair regeneration. We suggest that FGF5 not only mediates the activation of antioxidant pathways by cortisol, which constitutes a highly coordinated microenvironment in hair follicle cells, but also influences key signals of the Wnt pathway to regulate secondary hair follicle (SHF) development. Overall, our findings here demonstrate that FGF5 plays a significant role in regulating SHF growth in sheep and potentially serves as a molecular marker of fine wool growth in sheep breeding.
摘要：
成纤维细胞生长因子5（FGF5）在毛囊周期中促进从生长期到降生期的转变中起关键作用。绵羊是研究毛发生长的优秀模型，经常用于与人类皮肤病相关的各种研究过程中。我们使用CRISPR/Cas9系统来产生四只FGF5编辑的Dorper绵羊,并且在编辑的绵羊中仅检测到低水平的FGF5。GE绵羊的细羊毛密度明显增加，直径为14.4～20.0μm的细羊毛所占比例明显较高。基因编辑（GE）绵羊皮肤中的增殖信号强于野生型（WT）绵羊。FGF5编辑降低皮肤中的皮质醇浓度，进一步激活抗氧化酶的活性，如谷胱甘肽过氧化物酶（GSH-Px），并调节含有Wnt激动剂的Wnt信号通路的表达（Rspondins，Rspos）和拮抗剂（Notum）在头发再生中。我们建议FGF5不仅介导皮质醇对抗氧化途径的激活，这构成了毛囊细胞中高度协调的微环境，而且还影响Wnt通路的关键信号以调节次级毛囊（SHF）发育。总的来说,我们的发现表明，FGF5在调节绵羊SHF生长中起着重要作用，并可能作为绵羊育种中细羊毛生长的分子标记。
