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