Guan Wen, Yu Xiaolan, Li Jingjing, Deng Qing, Zhang Yang, Gao Jing, Xia Peng, Yuan Yunsheng, Gao Jin, Zhou Liang, Han Wei, Yu Yan
Shanghai Municipality Key Laboratory of Veterinary Biotechnology, Department of Animal Sciences, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai 200240, P.R. China.
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Exp Ther Med. 2017 Aug;14(2):1001-1008. doi: 10.3892/etm.2017.4578. Epub 2017 Jun 12.
Although hair loss or alopecia is a common disease, its exact mechanisms are not yet well understood. The present study investigated the hypothesis that the homeostatic regulation of genes during hair regeneration may participate in hair loss, based on the cyclicity of hair growth. A cluster of such genes was identified by an expression gene-array from the dorsal skin in a depilated mouse model, and CXCL4 was identified as a significantly regulated gene during the hair regeneration process. To elucidate the function of CXCL4 in hair growth, CXCL4 activity was blocked by the administration of an anti-CXCL4 monoclonal antibody (mAb). Histomorphometric analysis indicated that anti-CXCL4 mAb induced an earlier anagen phase and delayed hair follicle regression, in contrast with that in the control group. Moreover, CXCL4 mAb upregulated the transcription levels of several hair growth-related genes, including Lef1, Wnt10b, Bmp4 and Bmp2. In addition, CXCL4 mAb increased the levels of the proliferation-related protein PCNA and Bcl-2 during the anagen phase, while it reduced the expression of pro-apoptotic protein Bax and cleaved caspase-3 during the catagen phase. These findings reveal that CXCL4 plays an important role in hair growth, and that blockade of CXCL4 activity promotes hair growth.
尽管脱发或秃发是一种常见疾病,但其确切机制尚未完全明确。基于头发生长的周期性,本研究探讨了毛发再生过程中基因的稳态调节可能参与脱发的假说。在脱毛小鼠模型中,通过对背部皮肤进行表达基因芯片分析,鉴定出了一组此类基因,并且CXCL4被确定为毛发再生过程中显著调控的基因。为了阐明CXCL4在毛发生长中的功能,通过给予抗CXCL4单克隆抗体(mAb)来阻断CXCL4的活性。组织形态计量学分析表明,与对照组相比,抗CXCL4 mAb诱导了更早的生长期,并延迟了毛囊退化。此外,CXCL4 mAb上调了包括Lef1、Wnt10b、Bmp4和Bmp2在内的几种毛发生长相关基因的转录水平。另外,CXCL4 mAb在生长期增加了增殖相关蛋白PCNA和Bcl-2的水平,而在退行期降低了促凋亡蛋白Bax和裂解的caspase-3的表达。这些发现揭示了CXCL4在毛发生长中起重要作用,并且阻断CXCL4活性可促进毛发生长。