Yamagishi T, Nakajima Y, Miyazono K, Nakamura H
Department of Anatomy, Saitama Medical School, Japan.
J Cell Physiol. 1999 Jul;180(1):35-45. doi: 10.1002/(SICI)1097-4652(199907)180:1<35::AID-JCP4>3.0.CO;2-R.
In the early embryonic heart, endothelial cells in atrioventricular (AV) and outflow tract (OT) regions are transformed into the invasive mesenchymal cells that form endocardial cushion tissue (endothelial-mesenchymal transformation). It has been reported that bone morphogenetic proteins (BMPs) are transcribed in the AV and OT regions of the embryonic mouse heart. We previously reported that transforming growth factor beta 3 (TGFbeta3) triggers the initial phenotypic changes seen in endothelial-mesenchymal transformation. We cloned BMP2 from embryonic chick hearts and examined its functional role during endocardial cushion tissue formation. In situ hybridization showed BMP2 transcripts in the myocardium of the AV and OT regions, but not in endothelial/mesenchymal cells. Antisense oligodeoxynucleotides to BMP2 inhibited mesenchyme formation in AV endocardium cocultured with associated myocardium. This inhibitory effect was reversed by the addition of recombinant BMP2. In cultured AV endothelial monolayers, recombinant BMP2 did not induce any cellular phenotypic changes characteristic of endothelial-mesenchymal transformation. However, BMP2 enhanced the TGFbeta-induced initial phenotypic changes associated with endothelial-mesenchymal transformation. These results suggest that BMP2 1) plays an important role in the formation of endocardial cushion tissue and 2) acts synergistically with TGFbeta3 in the regulation of this developmental event.
在胚胎早期心脏中，房室（AV）和流出道（OT）区域的内皮细胞会转变为形成心内膜垫组织的侵袭性间充质细胞（内皮-间充质转化）。据报道，骨形态发生蛋白（BMPs）在胚胎小鼠心脏的AV和OT区域转录。我们之前报道过，转化生长因子β3（TGFβ3）触发内皮-间充质转化中最初出现的表型变化。我们从胚胎鸡心脏中克隆了BMP2，并研究了其在心内膜垫组织形成过程中的功能作用。原位杂交显示BMP2转录本存在于AV和OT区域的心肌中，但在内皮/间充质细胞中不存在。针对BMP2的反义寡脱氧核苷酸抑制了与相关心肌共同培养的AV心内膜中间充质的形成。添加重组BMP2可逆转这种抑制作用。在培养的AV内皮单层细胞中，重组BMP2未诱导出任何内皮-间充质转化特有的细胞表型变化。然而，BMP2增强了TGFβ诱导的与内皮-间充质转化相关的最初表型变化。这些结果表明，BMP2 1）在心内膜垫组织形成中起重要作用，2）在调节这一发育事件中与TGFβ3协同作用。
