Tanaka K, Oda N, Iwasaka C, Abe M, Sato Y
Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.
J Cell Physiol. 1998 Aug;176(2):235-44. doi: 10.1002/(SICI)1097-4652(199808)176:2<235::AID-JCP2>3.0.CO;2-P.
Ets-1, a transcription factor, is induced in endothelial cells (ECs) during angiogenesis. Here, we investigated the expression of Ets-1 during reendothelialization. When a confluent monolayer of human umbilical vein endothelial cell line, ECV304, was denuded, ECV304 at the wound edge expressed Ets-1. An immunohistochemical analysis revealed that Ets-1 accumulated in migrating cells at the wound edge and returned to basal level when reendothelialization was accomplished. This induction of Ets-1 could be reproduced in in vivo denudation of rat aortic endothelium by a balloon catheter. The induction of Ets-1 in ECs after denudation was regulated transcriptionally, and humeral factors released from injured ECs might not be responsible. Mitogen-activated protein kinase (MAPK) activities were investigated to explore the mechanism of this induction. Although extracellular signal-regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1 (JNK1), and p38 were activated after denudation, the activation of ERK1 and p38 was more rapid and prominent. PD98059, a specific MAPK/ERK kinase (MEK) 1 inhibitor, did not affect the induction of ets-1 mRNA, whereas SB203580, a specific p38 inhibitor, almost completely abrogated its induction. These results indicate that Ets-1 is induced in ECs after denudation through activation of p38. This induction of Ets-1 may be relevant for reendothelialization by regulating the expression of certain genes.
Ets-1是一种转录因子，在血管生成过程中在内皮细胞（ECs）中被诱导表达。在此，我们研究了再内皮化过程中Ets-1的表达情况。当人脐静脉内皮细胞系ECV304的汇合单层细胞被剥脱时，伤口边缘的ECV304细胞表达Ets-1。免疫组织化学分析显示，Ets-1在伤口边缘迁移的细胞中积累，而再内皮化完成后又恢复到基础水平。通过球囊导管对大鼠主动脉内皮进行体内剥脱，也能重现Ets-1的这种诱导现象。剥脱后ECs中Ets-1的诱导是由转录调控的，损伤的ECs释放的体液因子可能不起作用。我们研究了丝裂原活化蛋白激酶（MAPK）的活性，以探索这种诱导的机制。尽管细胞外信号调节蛋白激酶1/2（ERK1/2）、c-Jun氨基末端激酶1（JNK1）和p38在剥脱后被激活，但ERK1和p38的激活更为迅速和显著。特异性MAPK/ERK激酶（MEK）1抑制剂PD98059不影响ets-1 mRNA的诱导，而特异性p38抑制剂SB203580几乎完全消除了其诱导。这些结果表明，剥脱后ECs中Ets-1通过p38的激活而被诱导。Ets-1的这种诱导可能通过调节某些基因的表达与再内皮化相关。
