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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / cytology
  • Aorta, Thoracic / enzymology*
  • Aorta, Thoracic / injuries*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Catheterization / adverse effects
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology
  • Gene Expression Regulation, Enzymologic / physiology*
  • Growth Substances / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Male
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Umbilical Veins / cytology
  • Umbilical Veins / enzymology
  • p38 Mitogen-Activated Protein Kinases


  • ETS1 protein, human
  • Ets1 protein, rat
  • Growth Substances
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger
  • Transcription Factors
  • Protein-Tyrosine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases