Granulocyte/Macrophage Colony-Stimulating Factor Influences Angiogenesis by Regulating the Coordinated Expression of VEGF and the Ang/Tie System

Abstract

Granulocyte/macrophage colony-stimulating factor (GM-CSF) can accelerate wound healing by promoting angiogenesis. The biological effects of GM-CSF in angiogenesis and the corresponding underlying molecular mechanisms, including in the early stages of primitive endothelial tubule formation and the later stages of new vessel maturation, have only been partially clarified. This study aimed to investigate the effects of GM-CSF on angiogenesis and its regulatory mechanisms. Employing a self-controlled model (Sprague-Dawley rats with deep partial-thickness burn wounds), we determined that GM-CSF can increase VEGF expression and decrease the expression ratio of Ang-1/Ang-2 and the phosphorylation of Tie-2 in the early stages of the wound healing process, which promotes the degradation of the basement membrane and the proliferation of endothelial cells. At later stages of wound healing, GM-CSF can increase the expression ratio of Ang-1/Ang-2 and the phosphorylation of Tie-2 and maintain a high VEGF expression level. Consequently, pericyte coverages were higher, and the basement membrane became more integrated in new blood vessels, which enhanced the barrier function of blood vessels. In summary, we report here that increased angiogenesis is associated with GM-CSF treatment, and we indicate that VEGF and the Ang/Tie system may act as angiogenic mediators of the healing effect of GM-CSF on burn wounds.

The mRNA expressions and immunohistochemistry of factors involved in angiogenesis and lymphangiogenesis in the early stage of rat skin incision wounds

“…These factors have been reported to be involved in various types of angiogenesis [10,13,[16][17][18][29][30][31], and may be involved in the skin wound healing in our system.…”

“…In this study, we examined mRNA expressions of factors possibly involved in angiogenesis in the rat skin incision wounds, using TaqMan probes. The factors studied are: angiopoietin (ANGPT) 1 and 2 [6][7][8], cadherin 5 (CDH5) [9], granulocyte-macrophage colony stimulating factor (CSF2/GM-CSF) [10][11][12][13], granulocyte colony stimulating factor http://dx.doi.org/10.1016/j.legalmed.2015.02.007 1344-6223/Ó 2015 Elsevier Ireland Ltd. All rights reserved.…”

Spatial structural integrity is important for adipose regeneration after transplantation

“…Macrophages can secrete matrix metalloproteinases, which make tunnel-like structures in ischemic tissue and thereby provide space for angiogenesis [14]. Macrophages secrete various angiogenic growth factors such as vascular endothelial growth factor [28]. In this study, vessel density did not significantly differ between the two groups, although Fig.…”

Proteins in Preservation Fluid as Predictors of Delayed Graft Function in Kidneys from Donors after Circulatory Death

“…Furthermore, GM-CSF can stimulate tissue regeneration by promoting angiogenesis through activating VEGFmediated angiopoietin-Tie signaling (39). A synergetic role for GM-CSF and osteopontin in the recruitment of macrophages and monocytes to the implanted kidney, which promotes remodeling and better engraftment, is conceivable.…”