Induction of Ets-1 in endothelial cells during reendothelialization after denuding injury

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.