TGF-β1, -β2 and -β3 cooperate to facilitate tubulogenesis in the explanted quail heart

Jennifer S. Holifield, Angela M. Arlen, Raymond B Runyan, Robert J. Tomanek

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: Transforming growth factor-β (TGF-β) isoforms have been implicated as both pro- and anti-angiogenic modulators. In this study we addressed the roles of TGF-β isoforms on coronary tubulogenesis. Methods: 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. Results: Addition of any isoform (TGF-β1, TGF-β2 or TGF-β3) virtually prevented tubulogenesis (>95% inhibition), while stimulation of tubulogenesis occurred by adding neutralizing antibodies to TGF-β3, but not to TGF-β1 or -β2. When all three isoforms were added, tubulogenesis was enhanced, indicating the key role of TGF-β3. Documentation of the inhibitory effect of TGF-β 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-β1, -β2, or -β3 were added to the cultures. Conclusions: (1) TGF-β1, -β2 and -β3 each inhibits angiogenesis; (2) cooperation between the three TGF-β 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-βs.

Original languageEnglish (US)
Pages (from-to)491-498
Number of pages8
JournalJournal of Vascular Research
Volume41
Issue number6
DOIs
StatePublished - 2004

Fingerprint

Quail
Transforming Growth Factors
Protein Isoforms
Endothelial Cells
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Angiogenesis Inducing Agents
Neutralizing Antibodies
Documentation
Blood Vessels
Collagen
Gels

Keywords

  • Angiogenesis
  • Coronary tubulogenesis
  • Embryo
  • Quail heart explant model
  • Vasculogenesis

ASJC Scopus subject areas

  • Physiology

Cite this

TGF-β1, -β2 and -β3 cooperate to facilitate tubulogenesis in the explanted quail heart. / Holifield, Jennifer S.; Arlen, Angela M.; Runyan, Raymond B; Tomanek, Robert J.

In: Journal of Vascular Research, Vol. 41, No. 6, 2004, p. 491-498.

Research output: Contribution to journalArticle

Holifield, Jennifer S. ; Arlen, Angela M. ; Runyan, Raymond B ; Tomanek, Robert J. / TGF-β1, -β2 and -β3 cooperate to facilitate tubulogenesis in the explanted quail heart. In: Journal of Vascular Research. 2004 ; Vol. 41, No. 6. pp. 491-498.
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AB - Background: Transforming growth factor-β (TGF-β) isoforms have been implicated as both pro- and anti-angiogenic modulators. In this study we addressed the roles of TGF-β isoforms on coronary tubulogenesis. Methods: 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. Results: Addition of any isoform (TGF-β1, TGF-β2 or TGF-β3) virtually prevented tubulogenesis (>95% inhibition), while stimulation of tubulogenesis occurred by adding neutralizing antibodies to TGF-β3, but not to TGF-β1 or -β2. When all three isoforms were added, tubulogenesis was enhanced, indicating the key role of TGF-β3. Documentation of the inhibitory effect of TGF-β 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-β1, -β2, or -β3 were added to the cultures. Conclusions: (1) TGF-β1, -β2 and -β3 each inhibits angiogenesis; (2) cooperation between the three TGF-β 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-βs.

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