Xi-Qiao Wang, Ying-Kai Liu, Chun Qing, Shu-Liang Lu
Institute of Burn, Ruijin Hospital, Jiaotong University Medical School, 197 Ruijin Road, Shanghai, People's Republic of China.
Microvasc Res. 2009 Mar;77(2):204-11. doi: 10.1016/j.mvr.2008.08.007. Epub 2008 Sep 18.
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.
肥厚性瘢痕（HSc）有过多的微血管，其中大部分部分或完全闭塞。微血管内皮细胞积聚和微血管闭塞的潜在机制尚不清楚。在本研究中，我们用苏木精-伊红染色和电子显微镜观察微血管，并用免疫化学检测细胞因子表达。此外，我们从人肥厚性瘢痕组织和正常皮肤中分离成纤维细胞和内皮细胞，并研究它们的细胞因子表达。此外，我们检测了与正常内皮细胞共培养并用抗VEGF和抗bFGF中和抗体阻断时内皮细胞的增殖情况。结果显示，肥厚性瘢痕微血管中有更多的内皮细胞，且细胞肿胀。培养的肥厚性瘢痕成纤维细胞分泌的细胞因子明显更多，而肥厚性瘢痕内皮细胞分泌的细胞因子明显更少，细胞因子和胶原蛋白mRNA也有相同趋势，免疫化学结果也证实了这一点。此外，与肥厚性瘢痕成纤维细胞共培养时内皮细胞增殖更快，而抗VEGF和抗bFGF中和抗体可使其增殖减少。这是关于肥厚性瘢痕中内皮细胞功能的首次报道。细胞因子分泌和胶原蛋白产生的亢进在很大程度上导致了内皮细胞的过度增殖和功能衰退，两种细胞类型的功能失调都导致了微血管闭塞。
