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

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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.

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Authors and Affiliations

  1. Department of Pathology and Research Programs, University of Helsinki, POB 63, 00014, Helsinki, Finland

    Shentong Fang, Nalle Pentinmikko, Maritta Ilmonen & Petri Salven

  2. Biomedicum Helsinki, POB 63, 00014, Helsinki, Finland

    Petri Salven

Authors
  1. Shentong Fang
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  2. Nalle Pentinmikko
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  3. Maritta Ilmonen
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  4. Petri Salven
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Correspondence to Petri Salven.

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Shentong Fang and Nalle Pentinmikko contributed equally to this work.

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Fang, S., Pentinmikko, N., Ilmonen, M. et al. Dual action of TGF-β induces vascular growth in vivo through recruitment of angiogenic VEGF-producing hematopoietic effector cells. Angiogenesis 15, 511–519 (2012). https://doi.org/10.1007/s10456-012-9278-9

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  • DOI: https://doi.org/10.1007/s10456-012-9278-9

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