Document Detail


Ets-1 transcription is required in tissue factor driven microvessel formation and stabilization.
MedLine Citation:
PMID:  22869003     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Tissue factor (TF) has well-recognized roles as initiator of blood coagulation as well as an intracellular signaling receptor. TF signaling regulates gene transcription and protein translation. Recently, we have shown that TF-induced mature neovessel formation is ultimately driven by CCL2 expression. However, the signaling process induced by TF to promote microvessel formation remains to be determined. This study was designed with the objective to investigate the mechanisms involved in TF-induced neovessel formation. Here, we have identified that Ets-1 expression is a downstream effector of TF signaling. TF-siRNA induced a highly significant reduction in Ets-1 expression levels and in Ets-1/DNA binding while inducing abrogation of microvessel formation. Activation of Ets-1 rescued the effect of TF inhibition and restored microvessel formation confirming the critical role of Ets-1 in TF-induced angiogenesis. VE-cadherin expression, a key regulator of endothelial intercellular junctions, and an Ets-1 target molecule was dependent of TF-inhibition. We show that TF signals through ERK1/2 to activate Ets-1 and induce CCL2 gene expression by binding to its promoter region. We conclude that endothelial cell TF signals through ERK1/2 and Ets-1 to trigger microvessel formation.
Authors:
Gemma Arderiu; Esther Peña; Rosa Aledo; Sonia Espinosa; Lina Badimon
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-7
Journal Detail:
Title:  Angiogenesis     Volume:  -     ISSN:  1573-7209     ISO Abbreviation:  Angiogenesis     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9814575     Medline TA:  Angiogenesis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Cardiovascular Research Center (CSIC-ICCC), Hospital de Sant Pau (UAB), IIB-Sant Pau. CiberOBN, Instituto de Salut Carlos III, C/ Sant Antoni Mª Claret 167, 08025, Barcelona, Spain.
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