血管紧张素Ⅱ受体在人皮肤胚胎发育过程中的表达和意义

Expression of angiotensinⅡtype 1 and type 2 receptors during human skin development in fetus

目的观察血管紧张素Ⅱ(AngⅡ)1型(AT_1)受体和2型(AT_2)受体在人胎儿皮肤中的分布和表达量的动态变化,探讨其可能的生物学意义。方法用免疫荧光组织化学方法和实时定量PCR技术检测AT_1和AT_2受体在不同孕龄胎儿皮肤附件中的分布和表达量的变化。结果在11～13周龄的胎儿皮肤,可见较强的AT_2受体阳性标记信号,主要定位于胎儿表皮;几乎很难检测到AT_1受体阳性标记信号。在14～19周龄的胎儿皮肤表皮,可检测到微弱AT_1受体阳性信号。妊娠24周以后,AT_1受体的表达迅速增加,然而AT_2受体的表达逐渐下降。AT_1和AT_2受体在发育中的表皮、汗腺、真皮的微血管呈阳性标记。AT_1和AT_2受体在成人皮肤中的表达定位与胎儿无明显差异。实时定量PCR法结果显示,在妊娠的11～37周,均可检测到AT_1和AT_2受体mRNA,但主要表达的受体亚型是AT_2受体mRNA,随胚胎发育AT_2受体mRNA维持高表达。妊娠24周以后随胎龄增加AT_1受体mRNA表达增加,AT_2受体mRNA表达下降。在成人皮肤也可检测到AT_1和AT_2受体mRNA,但表达水平均较胎儿时期低。结论在皮肤胚胎发育过程中,AT_1和AT_2的表达呈现发育调节方式,这种独特的表达方式提示AngⅡ对皮肤形态发生和损伤修复可能的影响,深层次探讨AngⅡ及其受体AT_1和AT_2在胚胎发育中的作用,将有助于理解成人和胎儿皮肤创伤愈合不同结局的分子机制。

Objective To observe the distribution and expression change of angiotensin（Ang） Ⅱ receptor during fetal development of human skin. Methods The spatial and temporal changes of the expression of Ang Ⅱ type 1 （AT1） and type 2 （AT2） receptors in human developing skin at different gestational ages were investigated using immunofluoreseenee staining and real-time polymerase chain reaction （PCR）. Results In human fetal skin, the immunofluorescence labeling of both AT1 and AT2 receptors was mainly distributed in epidermal cells and sweat gland. Expression of AT2 receptors with intensely labeled immunosignal was first detected in the developing fetal epidermis from embryo gestational age （EGA）Ⅱ weeks. However, the immunofluorescence labeling of AT1 receptor was faint at early stage of gestation. From EGA 24 weeks, positive labeling of AT1 receptor increased, whereas positive labeling of AT2 receptor gradually decreased in the fetal skin. In addition, both AT1 and AT2 receptors were also detectable in adult skin tissues, with weak positive signals. These findings were further confirmed by real-time PCR. Conclusion AT1 and AT2 receptors are expressed in a developmentally regulated manner in human fetal skin, which may be related to various roles that Ang Ⅱ may play during skin embryonic development. This study could assist to understand the difference in skin tissue repair between fetus and adult.