下调间隙连接蛋白43表达对血管内皮细胞生物功能的影响

The effect of Connexin43 downregulation on biological functions of HUVEC

间隙连接蛋白43(Cx43)在伤口愈合过程中发挥重要作用。血管生成也是创伤修复的一个重要特征,但目前很少有关Cx43对血管内皮细胞功能影响的研究。本文采用小干扰RNA(si RNA)特异性减少Cx43在人脐静脉内皮细胞(HUVEC)的表达,研究Cx43的表达下调对HUVEC细胞间信号传递、活力、增殖、迁移以及血管生成活性的影响。结果表明,经si RNA处理后,HUVEC内Cx43的表达降低约80%(P<0.05),HUVEC细胞间信号传递功能减少约65%(P<0.05),细胞活力、增殖和迁移活性显著降低(P<0.05)、血管生成速度减缓。推测在创伤早期维持Cx43的低水平表达,抑制渗透性和炎性等异常血管的生成速度,是保证伤口愈合过程中各关键步骤协调进行的前提条件之一。

Connexin43 has been shown to play a pivotal role in wound healing process. Wound repair is enhanced by acute downregulation of connexin43, by increasing proliferation and migration of keratinocyte and fibroblast. Angiogenesis is also a central feature of wound repair, but little is known about the effects of connexin43 modulation on functions of endothelial cells. We used connexin43 specific small interference RNA （siRNA） to reduce the expression of connexin43 in human umbilical vein endothelial cell （HUVEC）, and investigated the effects of connexin43 downregulation on intercellular communication, viability, proliferation, migration and angiogenic activity of HUVEC. Treatment of siRNA markedly reduced the expression of connexin43 by ～80% in HUVEC （P〈0.05）, and decreased the intercellular communication by ～65% （P〈 0.05）. The viability, proliferation, migration and angiogenic activity of HUVEC decreased significantly （P 〈 0.05）, compared with that of the normal cells. The results suggest that temporally downregulation of connexin43 expression at early stage of wound to inhibit the abnormal angiogenesis characterized with leaky and inflamed blood vessels, maybe a prerequisite for coordinated normal healing process.