Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia.
Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia.
复制标题
Zyxin 表达增加及其在雄激素性脱发中的潜在功能
DOI：
10.3389/fcell.2020.582282
复制
发表时间：
2020
影响因子：
5.5
通讯作者：
Wu W
中科院分区：
文献类型：
--
作者：
Liu Q;Shi X;Zhang Y;Huang Y;Yang K;Tang Y;Ma Y;Zhang Y;Wang J;Zhang L;Zhang Q;Liu X;Lin J;Wang J;Wu W
雄激素性脱发（AGA）是最常见的进行性脱发形式，发生在一半以上的50岁男性中。毛囊（HF）小型化是AGA的一个特征，真皮乳头（DP）通过调节毛囊细胞活性在头发生长和再生中起关键作用。先前的研究表明，粘附信号是AGA发展的重要因素。Zyxin （ZYX）是一种肌动蛋白相互作用蛋白，对细胞粘附和迁移至关重要。本研究的目的是探讨ZYX在AGA中的表达及其潜在作用。实时聚合酶链反应（RT-PCR）分析显示，与未受影响的枕部HF相比，AGA患者受影响的额部HF中ZYX的表达升高。此外，免疫荧光染色也观察到DP内ZYX表达增加。我们的体内实验结果显示，与野生型小鼠相比，ZYX基因敲除小鼠的毛发生长和生长原进入能力增强。通过siRNA降低体外培养HFs中ZYX的表达，导致毛干生成增加，毛囊原进入延迟，真皮乳头细胞（DPCs）增殖增加，干细胞相关蛋白表达上调。这些结果在体外培养的DPCs中得到进一步验证。为了进一步揭示ZYX参与AGA的机制，我们通过RNA-seq分析鉴定了培养毛囊中ZYX siRNA处理后的基因特征。包括局灶黏附和HIF-1信号通路在内的多种途径被发现参与其中。综上所述，我们发现了ZYX在AGA患者患病额毛囊中的表达升高，并揭示了ZYX下调对小鼠体内、离体毛囊和体外DPC的影响。这些发现表明，ZYX在AGA的发病机制和DPC的干细胞特性中起重要作用，可能作为AGA的治疗靶点。
Androgenetic alopecia (AGA) is the most common progressive form of hair loss, occurring in more than half of men aged > 50 years. Hair follicle (HF) miniaturization is a feature of AGA, and dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Previous studies have revealed that adhesion signals are important factors in AGA development. Zyxin (ZYX) is an actin-interacting protein that is essential for cell adhesion and migration. The aim of this research was to investigate the expression and potential role of ZYX in AGA. Real-time polymerase chain reaction (RT-PCR) analysis revealed that ZYX expression was elevated in the affected frontal HF of individuals with AGA compared to unaffected occipital HF. Moreover, increased ZYX expression was also observed within DP using immunofluorescence staining. Our in vivo results revealed that ZYX knockout mice showed enhanced hair growth and anagen entry compared to wild-type mice. Reducing ZYX expression in ex vivo cultured HFs by siRNA resulted in the enhanced hair shaft production, delayed hair follicle catagen entry, increased the proliferation of dermal papilla cells (DPCs), and upregulated expression of stem cell-related proteins. These results were further validated in cultured DPCs in vitro. To further reveal the mechanism by which ZYX contributes to AGA, RNA-seq analysis was conducted to identify gene signatures upon ZYX siRNA treatment in cultured hair follicles. Multiple pathways, including focal adhesion and HIF-1 signaling pathways, were found to be involved. Collectively, we discovered the elevated expression of ZYX in the affected frontal hair follicles of AGA patients and revealed the effects of ZYX downregulation on in vivo mice, ex vivo hair follicles, and in vitro DPC. These findings suggest that ZYX plays important roles in the pathogenesis of AGA and stem cell properties of DPC and may potentially be used as a therapeutic target in AGA.
登录
查看更多内容
影响因子：
4.6
作者：
Yang CC;Cotsarelis G
通讯作者：
Cotsarelis G
影响因子：
6.5
作者：
Akiyama, M;Smith, LT;Shimizu, H
通讯作者：
Shimizu, H
影响因子：
4
作者：
Tucker, Richard P.;Ferralli, Jacqueline;Chiquet-Ehrismann, Ruth
通讯作者：
Chiquet-Ehrismann, Ruth
影响因子：
4.7
作者：
Ridgway, Rachel A.;Serrels, Bryan;Brunton, Valerie G.
通讯作者：
Brunton, Valerie G.
影响因子：
4.6
作者：
Yang, Yadong;Li, Yuanchao;Lu, Yuangang
通讯作者：
Lu, Yuangang