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Transforming growth factor-beta 1 (TGF-β1) induces angiogenesis through vascular endothelial growth factor (VEGF)-mediated apoptosis
Journal of cellular physiology, 2009-05, Vol.219 (2), p.449-458
Ferrari, Giovanni
Cook, Brandoch D.
Terushkin, Vitaly
Pintucci, Giuseppe
Mignatti, Paolo
2009
Details
Autor(en) / Beteiligte
Ferrari, Giovanni
Cook, Brandoch D.
Terushkin, Vitaly
Pintucci, Giuseppe
Mignatti, Paolo
Titel
Transforming growth factor-beta 1 (TGF-β1) induces angiogenesis through vascular endothelial growth factor (VEGF)-mediated apoptosis
Ist Teil von
Journal of cellular physiology, 2009-05, Vol.219 (2), p.449-458
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2009
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
VEGF and TGF‐β1 induce angiogenesis but have opposing effects on endothelial cells. VEGF protects endothelial cells from apoptosis; TGF‐β1 induces apoptosis. We have previously shown that VEGF/VEGF receptor‐2 (VEGFR2) signaling mediates TGF‐β1 induction of apoptosis. This finding raised an important question: Does this mechanism stimulate or inhibit angiogenesis? Here we report that VEGF‐mediated apoptosis is required for TGF‐β1 induction of angiogenesis. In vitro the apoptotic effect of TGF‐β1 on endothelial cells is rapid and followed by a long period in which the cells are refractory to apoptosis induction by TGF‐β1. Inhibition of VEGF/VEGFR2 signaling abrogates formation of cord‐like structures by TGF‐β1 with an effect comparable to that of z‐VAD, an apoptosis inhibitor. Similarly, genetic deficiency of VEGF abolishes TGF‐β1 upregulation of endothelial cell differentiation and formation of vascular structures in embryoid bodies. In vivo TGF‐β1 induces endothelial cell apoptosis as rapidly as in vitro. Inhibition of VEGF blocks TGF‐β1 induction of both apoptosis and angiogenesis, an effect similar to that of z‐VAD. Thus, TGF‐β1 induction of angiogenesis requires a rapid and transient apoptotic effect mediated by VEGF/VEGFR2. This novel, unexpected role of VEGF and VEGFR2 indicates VEGF‐mediated apoptosis as a potential target to control angiogenesis. J. Cell. Physiol. 219: 449–458, 2009. © 2009 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0021-9541
eISSN: 1097-4652
DOI: 10.1002/jcp.21706
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2749291
Format
–
Schlagworte
Animals
,
Apoptosis - physiology
,
Capillaries - anatomy & histology
,
Capillaries - physiology
,
Cattle
,
Cells, Cultured
,
Chickens
,
Chorioallantoic Membrane - blood supply
,
Chorioallantoic Membrane - metabolism
,
Endothelial Cells - cytology
,
Endothelial Cells - physiology
,
Endothelium, Vascular - cytology
,
Endothelium, Vascular - metabolism
,
Fibroblasts - cytology
,
Fibroblasts - physiology
,
Humans
,
In Situ Nick-End Labeling
,
Mice
,
Mice, Knockout
,
Neovascularization, Physiologic
,
Signal Transduction - physiology
,
Transforming Growth Factor beta1 - genetics
,
Transforming Growth Factor beta1 - metabolism
,
Vascular Endothelial Growth Factor A - genetics
,
Vascular Endothelial Growth Factor A - metabolism
,
Vascular Endothelial Growth Factor Receptor-1 - genetics
,
Vascular Endothelial Growth Factor Receptor-1 - metabolism
,
Vascular Endothelial Growth Factor Receptor-2 - genetics
,
Vascular Endothelial Growth Factor Receptor-2 - metabolism
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