Nagao Kaori, Taniyama Yoshiaki, Koibuchi Nobutaka, Morishita Ryuichi
Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
Biochem Biophys Res Commun. 2007 Aug 3;359(3):431-7. doi: 10.1016/j.bbrc.2007.05.140. Epub 2007 May 29.
During heart development, various signaling cascades are tightly regulated in a stage- and region-dependent manner. Vascular endothelial growth factor (VEGF) is one of the important molecules required for both vascular development and cardiac morphogenesis. VEGF receptors are present in the embryonic heart, so we focused on heart formation in VEGF-over-expressing Xenopus embryos. Over-expression of VEGF(170) caused disorganized vessels, while the expression of an endothelial marker, Tie-2, was increased. The embryo's heart was distinctly larger than that of control, and showed abnormal morphology. Histological analysis of these embryos showed failure of heart looping. In situ hybridization with Hand-1, which controls intrinsic morphogenetic pathways, revealed that the expression level of Hand-1 was decreased in the heart region. These results suggest that increased VEGF(170) levels disturb Hand-1 expression in the region required for normal heart morphogenesis. VEGF expression level may be important in heart morphology during embryonic development.
在心脏发育过程中，各种信号级联反应以阶段和区域依赖性方式受到严格调控。血管内皮生长因子（VEGF）是血管发育和心脏形态发生所需的重要分子之一。VEGF受体存在于胚胎心脏中，因此我们重点研究了VEGF过表达的非洲爪蟾胚胎的心脏形成。VEGF(170)的过表达导致血管紊乱，而内皮标记物Tie-2的表达增加。胚胎的心脏明显大于对照组，且形态异常。对这些胚胎的组织学分析显示心脏环化失败。用控制内在形态发生途径的Hand-1进行原位杂交，结果显示心脏区域Hand-1的表达水平降低。这些结果表明，VEGF(170)水平升高会干扰正常心脏形态发生所需区域的Hand-1表达。VEGF表达水平在胚胎发育过程中的心脏形态方面可能很重要。
