Galkowska Hanna, Wojewodzka Urszula, Olszewski Waldemar L
Department of Surgical Research and Transplantology, Medical Reasearch Center, Polish Academy of Sciences, Warsaw, Poland.
Wound Repair Regen. 2006 Sep-Oct;14(5):558-65. doi: 10.1111/j.1743-6109.2006.00155.x.
Keratinocytes and dermal endothelial cells, excluding leukocytes that infiltrate wounds, are the main source of soluble factors regulating healing of skin ulcers. We used immunohistochemistry to analyze the expression of various chemotactic and growth factors and their receptors in the margin of diabetic foot ulcers and in normal nondiabetic foot skin. Our study found significantly elevated expression of transforming growth factor-beta1 (TGF-beta1) and type I TGF-beta receptors (TGFbetaR1), granulocyte macrophage colony-stimulating factor (GM-CSF), and epidermal growth factor (EGF) in keratinocytes in the ulcer margin (p < 0.05). Significantly increased expression of monocyte chemotactic protein-1, GM-CSF, CXCR1, and TGFbetaRI and decreased expression of interleukin (IL)-10, IL-15, and TGF-beta1 were observed in ulcer dermal endothelial cells (p < 0.05). There was a lack of up-regulation of IL-8, CCR2A, IL-10 receptor, GM-CSF receptor, platelet-derived growth factors and their receptors, vascular endothelial growth factor and its type II receptor, EGF receptor, insulin-like growth factor-1, and nitric oxide synthase-2 in both KCs and endothelial cells in the ulcer. Finally, there was a lack of up-regulation of IL-10 and IL-15 in keratinocytes and of EGF, basic fibroblast growth factor, and nitric oxide synthase-3 in endothelial cells in the ulcer margins. The enhanced expression of some factors responsible for KC behavior could suggest an unimpaired capacity of keratinocytes to reepithelialize the margin of diabetic foot ulcers. However, lack of up-regulation of some angiogenic and leukocyte chemotactic factors, associated with the reduced influx of immune cells, may account for a poor formation of granulation tissue and chronicity of ulcer epithelialization.
角质形成细胞和真皮内皮细胞是调节皮肤溃疡愈合的可溶性因子的主要来源，不包括浸润伤口的白细胞。我们采用免疫组织化学方法分析了糖尿病足溃疡边缘和正常非糖尿病足皮肤中各种趋化因子、生长因子及其受体的表达。我们的研究发现，溃疡边缘角质形成细胞中转化生长因子-β1（TGF-β1）、I型TGF-β受体（TGFβR1）、粒细胞巨噬细胞集落刺激因子（GM-CSF）和表皮生长因子（EGF）的表达显著升高（p<0.05）。在溃疡真皮内皮细胞中观察到单核细胞趋化蛋白-1、GM-CSF、CXCR1和TGFβRI的表达显著增加，而白细胞介素（IL）-10、IL-15和TGF-β1的表达降低（p<0.05）。溃疡中的角质形成细胞和内皮细胞中IL-8、CCR2A、IL-10受体、GM-CSF受体、血小板衍生生长因子及其受体、血管内皮生长因子及其II型受体、EGF受体、胰岛素样生长因子-1和一氧化氮合酶-2均未上调。最后，溃疡边缘的角质形成细胞中IL-10和IL-15未上调，内皮细胞中EGF、碱性成纤维细胞生长因子和一氧化氮合酶-3也未上调。一些负责角质形成细胞行为的因子表达增强，可能提示角质形成细胞重新上皮化糖尿病足溃疡边缘的能力未受损。然而，一些血管生成和白细胞趋化因子未上调，与免疫细胞流入减少相关，可能是肉芽组织形成不良和溃疡上皮化慢性化的原因。
