Hypertrophic scar regression is linked to the occurrence of endothelial dysfunction.
Hypertrophic scar regression is linked to the occurrence of endothelial dysfunction.
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肥厚性疤痕消退与内皮功能障碍的发生有关
DOI：
10.1371/journal.pone.0176681
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Liu YK
中科院分区：
文献类型：
--
作者：
Wang XQ;Song F;Liu YK
在增生性瘢痕进展过程中，大多数微血管已被证明变得狭窄或完全闭塞。在这里，我们检查了毛细血管内皮细胞（EC）和成纤维细胞的形态学CD 31和α-平滑肌肌动蛋白（α-SMA）的免疫荧光染色和电子显微镜。另外，从瘢痕组织中分离内皮细胞和成纤维细胞，用ELISA法检测转化生长因子β 1（TGF-β1）、血小板衍生生长因子（PDGF）、内皮素1（ET-1）、血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）的水平。此外，我们评估了细胞活力，总胶原蛋白的生产，和细胞凋亡与EC条件培养基培养的增生性瘢痕来源的成纤维细胞。然后，将抗TGF-β1、抗PDGF、抗ET-1、抗VEGF和抗bFGF中和抗体分别加入EC培养基中，以鉴定哪种生长因子在抑制成纤维细胞生物学方面发挥更重要的作用。我们的研究结果表明，微血管管腔闭塞和EC萎缩的瘢痕发展过程中，特别是在退行性瘢痕（RS）。此外，EC生长因子分泌减少，并达到最低水平的RS。此外，根据培养结果，RS EC培养基抑制成纤维细胞活力和胶原蛋白的产生，并诱导细胞凋亡。TGF-β1、PDGF和bFGF在此过程中的作用较VEGF和ET-1更为重要。增生性瘢痕中发生的内皮功能障碍有助于成纤维细胞抑制和瘢痕消退，并且降低的TGF-β1、PDGF和bFGF水平在此过程中起关键作用。
Most microvessels have been shown to become stenosed or completely occluded during hypertrophic scar progression. Here, we examined the morphology of capillary endothelial cells (ECs) and fibroblasts using immunofluorescence staining for CD31 and alpha-smooth muscle actin (α-SMA) and electron microscopy. In addition, ECs and fibroblasts were isolated from scar tissues, and the levels of transforming growth factor beta 1 (TGF-β1), platelet-derived growth factor (PDGF), endothelin 1 (ET-1), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assayed using ELISAs. Furthermore, we assessed cell viability, total collagen production, and cell apoptosis in hypertrophic scar-derived fibroblasts cultured with EC-conditioned medium. Then, anti-TGF-β1, anti-PDGF, anti-ET-1, anti-VEGF, and anti-bFGF neutralising antibodies were individually added to the EC medium to identify which growth factor plays a more important role in inhibiting fibroblasts biology. Our results showed microvessel lumen occlusion and EC atrophy during scar development, particularly in regressive scars (RSs). Additionally, EC growth factor secretion decreased and reached the lowest levels in RSs. Furthermore, based on the culture results, RS EC medium inhibited fibroblast viability and collagen production and induced apoptosis. Moreover, TGF-β1, PDGF, and bFGF played more important roles in these processes than VEGF and ET-1. The endothelial dysfunction occurring in hypertrophic scars contributes to fibroblast inhibition and scar regression, and reduced TGF-β1, PDGF, and bFGF levels play key roles during this process.