Wen Chun Yang, Ito Masahiro, Chen Long-Dian, Matsuu Mutsumi, Shichijo Kazuko, Nakayama Toshiyuki, Nakashima Masahiro, Xu Zhao-Min, Ohtsuru Akira, Hsu Chao-Tien, Sekine Ichiro
Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
J Gastroenterol. 2003;38(5):431-5. doi: 10.1007/s00535-002-1078-3.
Angiogenesis is an important process in tissue development and wound healing. The Tie-2 receptor tyrosine kinases and ligands, angiopoietin (Ang)-1 and -2 have been postulated to play key roles in vascular development. The purpose of this study was to evaluate the expression of Tie-2 and Ang-1 and -2 in an acetic acid-induced gastric ulcer healing process in rats.
Gastric specimens were obtained at 0 (control), 1, 3, 5, 7, and 14 days after ulcer induction for reverse transcription polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical analysis.
Expression of Tie-2 and Ang-1 and -2 mRNAs was detected in normal gastric tissue and ulcerative tissues by RT-PCR. Western blot analysis revealed that Tie-2 expression reached a maximum on the third to fifth days. Expression of Ang-1 and -2 peaked on the first day. Ang-1 expression gradually became weaker in 2 weeks, whereas Ang-2 expression returned to normal in a few days. Immunohistochemically, Tie-2 was expressed constitutively in the endothelial cells of pre-existing vessels of the gastric wall, and Tie-2 expression was increased in the new capillaries of the ulcer base.
These findings suggest that Tie-2 and Ang-1 and -2 play an important role in angiogenesis in the early phase of ulcer healing.
血管生成是组织发育和伤口愈合中的一个重要过程。Tie-2受体酪氨酸激酶及其配体血管生成素(Ang)-1和-2被认为在血管发育中起关键作用。本研究旨在评估Tie-2、Ang-1和Ang-2在大鼠乙酸诱导的胃溃疡愈合过程中的表达。
在溃疡诱导后的0(对照)、1、3、5、7和14天获取胃标本,进行逆转录聚合酶链反应(RT-PCR)、蛋白质印迹分析和免疫组织化学分析。
通过RT-PCR在正常胃组织和溃疡组织中检测到Tie-2以及Ang-1和Ang-2 mRNA的表达。蛋白质印迹分析显示,Tie-2表达在第3至5天达到最高。Ang-1和Ang-2的表达在第1天达到峰值。Ang-1的表达在2周内逐渐减弱,而Ang-2的表达在数天内恢复正常。免疫组织化学结果显示,Tie-2在胃壁原有血管的内皮细胞中持续表达,且在溃疡底部的新毛细血管中Tie-2表达增加。
这些发现表明,Tie-2以及Ang-1和Ang-2在溃疡愈合早期的血管生成中起重要作用。