TGF-beta1, -beta2 and -beta3 cooperate to facilitate tubulogenesis in the explanted quail heart

Transforming growth factor-beta (TGF-beta) isoforms have been implicated as both pro- and anti-angiogenic modulators. In this study we addressed the roles of TGF-beta isoforms on coronary tubulogenesis. Embryonic (E6) quail ventricular specimens were explanted onto collagen gels allowing endothelial...

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Veröffentlicht in:Journal of vascular research 2004-11, Vol.41 (6), p.491-498
Hauptverfasser: Holifield, Jennifer S, Arlen, Angela M, Runyan, Raymond B, Tomanek, Robert J
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creator Holifield, Jennifer S
Arlen, Angela M
Runyan, Raymond B
Tomanek, Robert J
description Transforming growth factor-beta (TGF-beta) isoforms have been implicated as both pro- and anti-angiogenic modulators. In this study we addressed the roles of TGF-beta isoforms on coronary tubulogenesis. Embryonic (E6) quail ventricular specimens were explanted onto collagen gels allowing endothelial cells to migrate and form vascular tubes. Growth factors and/or neutralizing growth factor antibodies were added to the cultures. Endothelial cells were identified using a quail endothelial cell marker, QH1. Image analysis was used to quantify aggregate tube length. Addition of any isoform (TGF-beta(1), TGF-beta(2) or TGF-beta(3)) virtually prevented tubulogenesis (>95% inhibition), while stimulation of tubulogenesis occurred by adding neutralizing antibodies to TGF-beta(3), but not to TGF-beta(1) or -beta(2). When all three isoforms were added, tubulogenesis was enhanced, indicating the key role of TGF-beta(3). Documentation of the inhibitory effect of TGF-beta isoforms on tubulogenesis is further supported by our experiments in which the marked enhancement of tube formation by bFGF and VEGF was negated when exogenous TGF-beta(1), -beta(2), or -beta(3) were added to the cultures. (1) TGF-beta(1), -beta(2) and -beta(3) each inhibits angiogenesis; (2) cooperation between the three TGF-beta isoforms and other angiogenic factors is essential for the regulation of normal tubulogenesis and (3) the stimulatory effect of VEGF or bFGF on tubulogenesis is negated by exogenous TGB-betas.
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source Karger e-journals Complete Collection; MEDLINE; Alma/SFX Local Collection
subjects Animals
Antibodies - pharmacology
Coturnix
Fibroblast Growth Factor 2 - pharmacology
Heart - drug effects
Heart - embryology
Heart - physiology
Neovascularization, Physiologic - drug effects
Organ Culture Techniques
Transforming Growth Factor beta - immunology
Transforming Growth Factor beta - pharmacology
Transforming Growth Factor beta1
Transforming Growth Factor beta2
Transforming Growth Factor beta3
Vascular Endothelial Growth Factor A - pharmacology
title TGF-beta1, -beta2 and -beta3 cooperate to facilitate tubulogenesis in the explanted quail heart
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