title: 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.
authors.affiliation: Department of Burns, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Burns, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Burns, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shu
authors.affiliation: Department of Burns, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Burns, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Burns, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Julin
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Burns, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Shaohai
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Burns, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D002056:Burns / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics*; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D042764:Receptors, TIE / Q000235:genetics* / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D042764:Receptors, TIE; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9