Hyperactivity of fibroblasts and functional regression of endothelial cells contribute to microvessel occlusion in hypertrophic scarring.
Hypertrophic scars (HSc) have an excess of microvessels, most of which are partially or totally occluded. The mechanisms underlying microvessel endothelial cell accumulation and microvessel occlusion are poorly understood. In this study, we observed the microvessels with H&E staining and electron microscopy, and detected the cytokine expression with immunochemistry. In addition, we isolated fibroblasts and endothelial cells from both human HSc tissue and normal skin and studied their cytokine expression. Furthermore, we assayed the endothelial cell proliferation when co-cultured with normal endothelial cells and blocked with anti-VEGF and anti-bFGF neutralizing. The results revealed that more endothelial cells in HSc microvessels and the cells were swollen. The cultured HSc fibroblasts secreted significantly more while HSc endothelial cells secreted significantly less cytokines, and the same trend was found with cytokines and collagen mRNAs, which was also confirmed by immunochemistry finding. In addition, endothelial cells proliferated faster when co-cultured with HSc fibroblasts, and reduced by anti-VEGF and anti-bFGF neutralizing. This is the first report regarding the function of endothelial cells in hypertrophic scars. The hyperactivity in cytokine secretion and collagen production is largely responsible for over-proliferation and functional regression of endothelial cells, and the malfunctioning of both cell types contributes to microvessel occlusion.
Xi-Qiao
Wang
W
Institute of Burn, Ruijin Hospital, Jiaotong University Medical School, 197 Ruijin Road, Shanghai, People's Republic of China.
Ying-Kai
Liu
L
Chun
Qing
Q
Shu-Liang
Lu
L
D001483:Base Sequence; D049109:Cell Proliferation; D017439:Cicatrix, Hypertrophic / Q000378:metabolism* / Q000473:pathology*; D018920:Coculture Techniques; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D017931:DNA Primers; D019332:Endothelin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D003094:Collagen