miR-127-3p激活TGF-β调节毛囊周期性循环

Alopecia is a common disease in clinic which has few effective treatments. With the elevation of people’s living standard, everyone wants to attain beautiful and healthy hair. To produce new hairs, existing follicles undergo cycles of growth (anagen), regression (catagen) and rest (telogen). Hair follicles play an important role during hair cycle. Current researches focus on the interaction of these factors, and their signal transduction pathways. It was found that transforming growth factor-β (TGF-β) played an important role during hair cycle. TGF-b1 is involved in the regulation of catagen, possibly by the induction of apoptosis and the inhibition of proliferation of hair follicle keratinocytes. TGF-β2 suppresses proliferation of epithelial cells and stimulates synthesis of certain caspases. Then TGF-β2 triggers the intrinsic caspase network and subsequently epithelial cells are eliminated through apoptotic cell death. Recent data demonstrated that miRNA/mRNA regulatory networks are involved in the control of skin development, epidermal homeostasis, hair cycle-associated tissue remodeling and pigmentation. Recent study found that miR-127-3p suppressed glioblastoma cell growth by inhibiting tumor-promoting SKI and activating the tumor suppression effect of TGF-β signaling. So miR-127-3p was thought to regulate hair cycle through TGF-β signaling pathway. This project consists of two parts: (1) The expression of miR-127-3p and TGF-β during mouse hair cycle, (2) The effects of miR-127-3p for the regulation of hair cycle through TGF-β signaling in vivo and in vitro will be observed by using gene transfection and RNA interference technology. The result of this study can not only lead to a better understanding of the role and mechanism of miR-127-3p during hair cycle, but also it will contribute to the development of new therapeutic approaches for alopecia by using miRNA-based interventions.

毛发疾病是临床的常见病和多发病，但在治疗上缺乏非常有效的方法。毛发的生长与脱落取决于毛囊周期性的生长。国内外的研究均提示：毛发生长不仅仅受一两个因子的调控，这些因子是以一个复杂的网络系统来调节毛发的生长。TGF-β被证实对调控毛囊的形态学发生和周期性循环起着非常重要的作用。而最近有研究表明，miR-127-3p在胶质瘤细胞中低表达，其激活TGF-β抑制肿瘤增长，但其在毛发周期中的作用尚未知。本研究拟（1）通过小鼠毛发周期模型来研究miR-127-3p及TGF-β在皮肤或毛囊表达；（2）运用基因转染、RNA干扰等技术，在体内、外研究miR-127-3p对TGF-β信号通路的影响及其对毛囊周期的影响。本项目的研究结果不仅可以明确miR-127-3p通过激活TGF-β信号通路调节毛囊生长的分子机制，还将有助于从microRNA水平阐述毛发周期调节的分子网络，为开发防治脱发的新型药物提供依据。

毛发疾病是临床的常见病和多发病，但在治疗上缺乏非常有效的方法。毛发的生长与脱落取决于毛囊周期性的生长。国内外的研究均提示：毛发生长不仅仅受一两个因子的调控，这些因子是以一个复杂的网络系统来调节毛发的生长。TGF-β被证实对调控毛囊的形态学发生和周期性循环起着非常重要的作用。而最近有研究表明，miR-127-3p在胶质瘤细胞中低表达，其激活TGF-β抑制肿瘤增长，但其在毛发周期中的作用尚未知。本研究内容：（1）通过小鼠毛发周期模型来研究miR-127-3p及TGF-β在皮肤或毛囊表达；（2）运用基因转染、RNA干扰等技术，在体内、外研究miR-127-3p对TGF-β信号通路的影响及其对毛囊周期的影响。.研究结果：.体外研究：1.体内实验部分在角质细胞，成纤维细胞系中，检测其miR-127本底表达量，发现HACAT的miR127表达量很低，皮肤成纤维细胞无表达。后期试验只能进行过表达的研究。2.采用慢病毒转染的方法将miR-127-3p过表达，构建并筛选得到稳转细胞系。3.miR127-3p过表达细胞系的细胞骨架的合成增加；TGF-β表达明显增加；CCK-8、Edu显示下降、Ki67表达下降；凋亡相关基因p53及Bax表达明显增加；细胞周期相关基因PCNA及CyclinD表达受到抑制。.体内研究：1.成功构建小鼠毛发周期的模型。2.使用广州锐博的micrOFFTM技术，局部皮下注射antagomiR127-3p，初步发现其对于毛发生长的影响。3.皮下注射antagomiR127-3p于小鼠背部皮肤5d和8d组对TGF-β、β-catenin表达有抑制作用；增殖相关Ki67的表达有增高；对凋亡相关p53及Bax表达抑制；对细胞周期相关PCNA及CyclinD1表达有增加。.本研究结果从microRNA水平阐述毛发周期调节的分子网络，为开发防治脱发的新型药物提供了一定的依据。