angiogenin and Burns

Deep burn wounds have a high tendency to form hypertrophic scars. Previously, we found that angiogenin promoted neovascularization during deep burn wound healing. However, the association between angiogenin and scar formation is unclear.. We obtained human burn scar tissues from patients who underwent scar surgery and examined the role of angiogenin in scar tissues and determined its effects in scar fibroblasts and on transforming growth factor β1 (TGF-β1) secretion.. Our results showed an inverse correlation between angiogenin expression and scar severity. Next, we examined the effects of angiogenin in scar fibroblasts. We found that angiogenin was persistently expressed in human scar fibroblasts and that angiogenin expression significantly increased with time in the culture medium of scar fibroblasts. Treatment of scar fibroblasts with recombinant angiogenin significantly decreased their proliferation and TGF-β1 secretion. Moreover, angiogenin inhibited TGF-β1-mediated Smad2 signaling pathway.. Our data suggest a negative role of angiogenin in fibroblast proliferation via TGF-β1-mediated Smad2 signaling pathway.

Topics: Biomarkers; Burns; Cell Proliferation; Cells, Cultured; Cicatrix, Hypertrophic; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; Humans; In Vitro Techniques; Injury Severity Score; Male; Ribonuclease, Pancreatic; Sensitivity and Specificity; Smad2 Protein; Transforming Growth Factor beta1; Wound Healing

Burn blister fluid contains several angiogenic factors to promote wound neovascularization. In our previous study, we found that deep partial-thickness burn (DPTB) wounds showed higher expression levels of angiogenin to enhance vascularization compared with superficial partial-thickness burn wounds. Neovascularization is a complex process that involves an interaction between circulating angiogenic cells and mediators. We hypothesized that in addition to angiogenic factors burn blisters may contain specific cell types. The aim of the present study was to characterize the specific cells present in burn blisters.. Twenty-four burn blister fluid samples were obtained with informed consent from patients with superficial partial-thickness burn (n = 16) or DPTB (n = 8) wounds. Blister cells were isolated from individual intact blisters and characterized with flow cytometry analysis using CD14, CD34, vascular endothelial growth factor receptor 2, and CD133 markers. CD14 and CD34 blister cells were also isolated using a magnetic-activated cell sorting system to examine their potential for endothelial differentiation. Angiogenin levels in the burn blister fluids were evaluated with enzyme-linked immunosorbent assay.. CD14 cells were the most highly represented cell type in the burn fluids of both groups, although a significantly greater percentage of CD14 cells were observed in DPTB fluids. CD14 blister cells had a higher potency to differentiate into functional endothelial cells as compared with CD34 cells. The proportion of CD14 cells gradually increased after burn injury. In contrast to CD14 cells, angiogenin showed the highest expression levels at day 1 postburn. With regard to burn wound neovascularization, angiogenin expression was partially correlated with CD14 blister cells in the burn fluids.. We provide the first report on the characterization of blister cells in burn fluids. Our data suggest that CD14 blister cells may play a role in burn wound neovascularization. Measurement of CD14 blister cells serves as a possible tool for assessing burn wound status.

Topics: Adult; Biomarkers; Blister; Burns; Cell Differentiation; Cells, Cultured; Cohort Studies; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Female; Humans; Injury Severity Score; Lipopolysaccharide Receptors; Male; Neovascularization, Physiologic; Ribonuclease, Pancreatic; Sensitivity and Specificity; Wound Healing

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.

Topics: Animals; Burns; Cell Proliferation; Endothelial Cells; Gene Expression Regulation; Granulocyte-Macrophage Colony-Stimulating Factor; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neovascularization, Physiologic; Pericytes; Phosphorylation; Rats; Receptors, TIE; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A; Wound Healing