cgVEGF164基因对小鼠毛囊生长的影响

血管内皮生长因子(vascular endothelial growth factor, VEGF)是一种二聚体糖蛋白,能够诱导毛囊血管内皮细胞的增殖和迁移,调节毛囊周围毛细血管生成,进而影响毛囊的生长发育。已知cgVEGF164是绒山羊VEGF-A基因的一种主要剪接变体,但cgVEGF164基因是否具有调控毛囊生长发育的作用目前尚不清楚。为初步探究cgVEGF164基因对毛囊生长的影响及其机制,本研究通过原核显微注射制备cgVEGF164转基因过量表达小鼠。通过HE染色法比较转基因小鼠和非转基因对照小鼠毛囊的直径和密度,利用WesternBlot检测小鼠背部皮肤中信号蛋白ERK1/2、AKT1、LEF1的磷酸化水平。本研究成功获得5只阳性cg VEGF164转基因小鼠(雌雄比为4:1,阳性率8.5%);与非转基因对照小鼠相比,转基因小鼠毛囊直径增大、密度增加;经检测转基因小鼠中ERK1/2、AKT1、LEF1的磷酸化水平均上调。结果表明,cgVEGF164基因具有促进小鼠毛囊生长的作用,推测该功能可能与cgVEGF164影响ERK1/2、AKT1和LEF1等信号蛋白的磷酸化有关。

The effect of cgVEGF164 on the growth of murine hair follicles

Vascular endothelial growth factor(VEGF)is a dimeric glycoprotein that induces proliferation and migration of vascular endothelial cells as well as regulation of capillary formation around hair follicles which affects the growth and development of hair follicles.cgVEGF164 is a major splice variant of the cashmere goat VEGF-A gene,but its regulation on hair follicles is rarely known.In order to investigate the role of cgVEGF164 on the growth of murine hair follicles,we produced keratin 14 promoter-driven cgVEGF164 transgenic mice via pronuclear microinjection.Firstly,the diameter and density of hair follicles of transgenic mice were compared with non-transgenic control mice in paraffin sections stained by hematoxylin-eosin(H&E).Then,protein expression levels and the phosphorylation of ERK1/2,AKT1 and LEF1 were examined by Western blot.There are five positive individuals among the neonatal mice(positive rate is 8.5%).Compared with non-transgenic control mice,the diameter and density of hair follicles in transgenic mice are both obviously increased.The expression levels of P-ERK1/2/ERK1/2,P-AKT1/AKT1 and P-LEF1/LEF1 are significantly higher in transgenic mice than those in non-transgenic control mice.Based on these results,we conclude that cgVEGF164 as a growth factor can improve the growth of hair follicles which might be mediated by increasing the levels of ERK1/2,AKT1,and LEF1 protein phosphorylation.