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Angiogenesis

, Volume 15, Issue 3, pp 511–519 | Cite as

Dual action of TGF-β induces vascular growth in vivo through recruitment of angiogenic VEGF-producing hematopoietic effector cells

  • Shentong Fang
  • Nalle Pentinmikko
  • Maritta Ilmonen
  • Petri SalvenEmail author
Original Paper

Abstract

The role of Transforming growth factor β (TGF-β) as a regulator of blood vessel endothelium is complicated and controversial, and the mechanisms by which TGF-β is able to induce angiogenesis in vivo are not well understood. Here we show that TGF-β causes in vivo a massive recruitment of tissue infiltrating hematopoietic cells. Concurrently, TGF-β induces strong vascular endothelial growth factor (VEGF) production in the recruited hematopoietic cells, resulting in activated angiogenesis and vascular remodeling. TGF-β also promoted abnormalities of α-smooth muscle actin-expressing pericytes on angiogenic capillaries. TGF-β-induced angiogenic effect was inhibited by a systemic treatment with VEGF-neutralizing antibodies. When studied in isolated human hematopoietic cells, physiological concentrations of TGF-β stimulated VEGF mRNA and protein expression in a dose- and time-dependent manner. This induction was p38 and p44/p42 mitogen activated kinase dependent. p38 and p44/p42 activation was also observed in vivo in TGF-β–treated angiogenic murine tissues. Taken together, our results provide a dual action mechanism by which TGF-β promotes angiogenesis in vivo via recruitment of paracrine VEGF-expressing hematopoietic effector cells. This mechanism may activate vascular growth and remodeling during inflammatory conditions and tumor growth when TGF-β activity is upregulated.

Keywords

TGF-β VEGF Angiogenesis Hematopoietic Paracrine 

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Shentong Fang
    • 1
  • Nalle Pentinmikko
    • 1
  • Maritta Ilmonen
    • 1
  • Petri Salven
    • 1
    • 2
    Email author
  1. 1.Department of Pathology and Research ProgramsUniversity of HelsinkiHelsinkiFinland
  2. 2.Biomedicum HelsinkiHelsinkiFinland

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