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.
Tanaka
K
K
Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.
Oda
N
N
Iwasaka
C
C
Abe
M
M
Sato
Y
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000201:enzymology* / Q000293:injuries*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002404:Catheterization / Q000009:adverse effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases
C494041:ETS1 protein, human; C494043:Ets1 protein, rat; D006133:Growth Substances; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases