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Wound Healing Activity of Phage-Sisplayed TGF-β1 Model Peptide in Streptozotocin-Induced Diabetic Rats
International Journal of Peptide Research and Therapeutics ( IF 2.0 ) Pub Date : 2021-01-03 , DOI: 10.1007/s10989-020-10152-1
Hong Du , Duyin Jiang , Guodong Song , Chunyan Cao , Dong Zhang , Panxi Yu , Chenzhi Lai , Xiaoshuang Guo , Xianlei Zong , Xiaolei Jin

Objective

To evaluate the effect of phage-displayed TGF-β1 model peptide on cutaneous wound healing in streptozotocin-induced diabetic rats.

Methods

Full-thickness excisional wounds were made on the dorsums of 50 rats which were then randomly divided into five groups: negative control group (normal saline (NS)), two TGF-β1 control groups which were respectively treated with low-dose TGF-β1 ( 5 ng/ml) and high-dose TGF-β1 (50 ng/ml), and two model-peptide-treated groups which were respectively treated with low-dose model peptide ( 5 ng/ml,) and high-dose model peptide (50 ng/ml). At day 14 post-injury, rats were euthanised and wounds were assessed by gross, histopathology, immunohistochemistry, immunofluorescence and quantificational real-time polymerase chain reaction.

Results

A significant increase in rate of wound closure was observed in model peptide groups in comparison to negative control group. The results of histopathological staining revealed that re-epithelization and collagen deposition in model-peptide-treated groups were significantly higher than those in negative control group. The results of immunohistochemistry and immunofluorescence tests showed that Ki67-positive, VEGFA-positive, CD31-positive, α-SMA-positive, CD206-positive cells in model peptide and TGF-β1 control groups were more than those in negative control group. Furthermore, comparing with the mRNA expression profile in negative control groups, mRNA expression profile in model peptide group showed a decrease in proinflammatory cytokine and an increase in anti-inflammatory cytokine and collagen.

Conclusions

Phage-displayed TGF-β1 peptide facilitates wound healing through accelerating re-epithelialization, enhancing collagen deposition, promoting neo-vascularization, and inhibiting inflammatory response. Model peptide possesses the potential to be a promising treatment strategy for enhancing diabetic wound repair.



中文翻译:

噬菌体沉默的TGF-β1模型肽在链脲佐菌素诱导的糖尿病大鼠中的伤口愈合活性

目的

为了评估噬菌体展示的TGF-β1模型肽对链脲佐菌素诱导的糖尿病大鼠皮肤伤口愈合的作用。

方法

对50只大鼠的背部进行全层切除伤口,然后将其随机分为五组:阴性对照组(生理盐水(NS)),两个TGF-β1对照组,分别用低剂量TGF-β1治疗(5 ng / ml)和高剂量TGF-β1(50 ng / ml),以及两个模型肽治疗组,分别用低剂量模型肽(5 ng / ml)和高剂量模型处理肽(50 ng / ml)。损伤后第14天,对大鼠实施安乐死,并通过肉眼,组织病理学,免疫组织化学,免疫荧光和定量实时聚合酶链反应评估伤口。

结果

与阴性对照组相比,在模型肽组中观察到伤口闭合率显着增加。组织病理学染色的结果显示,模型肽治疗组的再上皮形成和胶原蛋白沉积显着高于阴性对照组。免疫组织化学和免疫荧光测试结果表明,模型肽和TGF-β1对照组的Ki67阳性,VEGFA阳性,CD31阳性,α-SMA阳性,CD206阳性细胞均大于阴性对照组。此外,与阴性对照组的mRNA表达谱相比,模型肽组的mRNA表达谱显示促炎细胞因子减少,抗炎细胞因子和胶原蛋白增加。

结论

噬菌体展示的TGF-β1肽通过加速重新上皮形成,增强胶原蛋白沉积,促进新血管形成和抑制炎症反应而促进伤口愈合。模型肽具有潜力成为增强糖尿病伤口修复的有前途的治疗策略。

更新日期:2021-01-03
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