Fibroblasts derived from chronic diabetic ulcers differ in their response to stimulation with EGF, IGF-I, bFGF and PDGF-AB compared to controls
Fibroblasts derived from chronic diabetic ulcers differ in their response to stimulation with EGF, IGF-I, bFGF and PDGF-AB compared to controls
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DOI：
10.1078/0171-9335-00228
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发表时间：
2002-03-01
影响因子：
6.6
通讯作者：
Mekkes, JR
中科院分区：
文献类型：
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作者：
Loots, MAM;Kenter, SB;Mekkes, JR
患有糖尿病的患者经历受损的伤口愈合，通常导致慢性足部溃疡。愈合可以通过应用生长因子如血小板衍生生长因子（PDGF）来加速。我们研究了从糖尿病性溃疡、非糖尿病性溃疡、非病变糖尿病性溃疡和年龄匹配对照培养的成纤维细胞对重组人PDGF-AB、表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）和胰岛素样生长因子（IGF-I）的促有丝分裂反应，通过[H]胸苷掺入测定。我们确定了这些因素的最佳浓度，并研究了同时或顺序加入的单一因素或因素组合诱导最高的促有丝分裂反应。对于单一生长因子添加，在所有成纤维细胞群体中观察到对不同生长因子的促有丝分裂反应的显著差异，PDGF-AB始终诱导最高反应，IGF-I最低（p小于或等于0.043）。IGF-I在糖尿病溃疡成纤维细胞中仅产生超过对照的1.7倍刺激，而慢性溃疡为2.95倍，非病变为3.2倍（p = 0.007），年龄匹配的成纤维细胞为5倍（p = 0.007）。EGF诱导的最高促有丝分裂反应在慢性溃疡成纤维细胞中明显低于年龄匹配的非病变对照组（p < 0.03），慢性溃疡成纤维细胞也需要显着更多的EGF才能达到这种最佳刺激（p < 0.02相对于年龄匹配和非损伤对照）。PDGF-IGF-I和FGF-PDGF对糖尿病溃疡成纤维细胞的刺激反应均高于序贯添加（p < 0.05）。此外，在IGF-I之前加入bFGF、PDGF-AB和EGF，与以相反顺序组合相比，在所有成纤维细胞中诱导更高的[3 H]胸苷摄取。当将具有最高刺激反应的生长因子组合（同时添加PDGF-IGF-I、FGF-PDGF和EGF-PDGF）与双倍剂量的PDGF进行比较时，观察到显著差异，其中组合PDGF-IGF-I的平均等级最高（p = 0.018）。总之，PDGF-AB和IGF-I的组合可能比PDGF-AB单独用于慢性糖尿病伤口更有用。
Patients with diabetes mellitus experience impaired wound healing, often resulting in chronic foot ulcers. Healing can be accelerated by application of growth factors like platelet-derived growth factor (PDGF). We investigated the mitogenic responses, measured by (3)[H]thymidine incorporation, of fibroblasts cultured from diabetic ulcers, non-diabetic ulcers, and non-lesional diabetic and age-matched controls, to recombinant human PDGF-AB, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-I). We determined the optimal concentration of these factors and investigated which single factor, or combination of factors, added simultaneously or sequentially, induced the highest mitogenic response. For single growth factor additions, in all fibroblast populations significant differences in mitogenic response to different growth factors were observed, with PDGF-AB consistently inducing the highest response and IGF-I the lowest (p less than or equal to 0.043). IGF-I produced only a 1.7-fold stimulation over control in diabetic ulcer fibroblasts, versus 2.95-fold for chronic ulcer, 3.2-fold for non-lesional (p = 0.007) and 5-fold for age-matched fibroblasts (p = 0.007). The highest mitogenic response induced by EGF was significantly less for chronic ulcer fibroblasts compared with age-matched and non-lesional controls (p < 0.03), chronic ulcer fibroblasts also needed significantly more EGF to reach this optimal stimulus (p < 0.02 versus age-matched and non-lesional controls).The simultaneous addition of FGF-IGF-I, PDGF-IGF-I and FGF-PDGF to diabetic ulcer fibroblasts always produced a higher stimulatory response than sequential additions (p < 0.05). Also the addition of bFGF, PDGF-AB and EGF prior to IGF-I induced a higher (3)[H]thymidine uptake in all fibroblasts compared to the combination of each in reverse order. Significant differences were observed when comparing the combinations of growth factors with the highest stimulatory responses (PDGF-IGF-I, FGF-PDGF and EGF-PDGF added simultaneously) to a double dose of PDGF, with the highest mean rank for the combination PDGF-IGF-I (p = 0.018). In conclusion, combinations such as PDGF-AB and IGF-I may be more useful than PDGF-AB alone for application in chronic diabetic wounds.