[en] Global inhibition of class I and II histone deacetylases (HDACs) impairs angiogenesis. Herein, we have undertaken the identification of the specific HDAC(s) with activity that is necessary for the development of blood vessels. Using small interfering RNAs, we observed that HDAC7 silencing in endothelial cells altered their morphology, their migration, and their capacity to form capillary tube-like structures in vitro but did not affect cell adhesion, proliferation, or apoptosis. Among several factors known to be involved in angiogenesis, platelet-derived growth factor-B (PDGF-B) and its receptor (PDGFR-beta) were the most upregulated genes following HDAC7 silencing. We demonstrated that their increased expression induced by HDAC7 silencing was partially responsible for the inhibition of endothelial cell migration. In addition, we have also shown that treatment of endothelial cells with phorbol 12-myristate 13-acetate resulted in the exportation of HDAC7 out of the nucleus through a protein kinase C/protein kinase D activation pathway and induced, similarly to HDAC7 silencing, an increase in PDGF-B expression, as well as a partial inhibition of endothelial cell migration. Collectively, these data identified HDAC7 as a key modulator of endothelial cell migration and hence angiogenesis, at least in part, by regulating PDGF-B/PDGFR-beta gene expression. Because angiogenesis is required for tumor progression, HDAC7 may represent a rational target for therapeutic intervention against cancer.
Disciplines :
Hematology Cardiovascular & respiratory systems
Author, co-author :
Mottet, Denis ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases
Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases
Pirotte, Sophie ; Université de Liège - ULiège > Labo de recherche sur les métastases
Waltregny, David ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases
Deroanne, Christophe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Lamour, Virginie ; Université de Liège - ULiège > Centre facultaire de rech. en cancérologie expérimentale
Lidereau, Rosette
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Language :
English
Title :
Histone deacetylase 7 silencing alters endothelial cell migration, a key step in angiogenesis
Publication date :
07 December 2007
Journal title :
Circulation Research
ISSN :
0009-7330
eISSN :
1524-4571
Publisher :
Lippincott Williams & Wilkins, Philadelphia, United States - Pennsylvania
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