Exosomes derived from autologous dermal fibroblasts promote diabetic cutaneous wound healing through the Akt/β-catenin pathway
Exosomes derived from autologous dermal fibroblasts promote diabetic cutaneous wound healing through the Akt/β-catenin pathway
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DOI：
10.1080/15384101.2021.1894813
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发表时间：
2021-03-06
期刊：
影响因子：
4.3
通讯作者：
Xu, Wenrong
中科院分区：
文献类型：
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作者：
Han, Xinye;Wu, Peipei;Xu, Wenrong
糖尿病皮肤创面是糖尿病的并发症之一，目前难以治愈。自体真皮成纤维细胞(DFS)在皮肤再生和修复方面显示出巨大的潜力。然而，从自体真皮成纤维细胞(DF-Ex)衍生的外切体是否可以用于加速糖尿病皮肤伤口的愈合尚不清楚。本研究采用高糖处理人脐静脉内皮细胞(HUVECs)。我们发现DF-Ex可以逆转高糖对体外培养的人脐静脉内皮细胞的损伤。采用高脂饮食和链脲佐菌素建立2型糖尿病(T2 DM)大鼠模型，建立T2 DM大鼠皮肤创面模型。我们发现皮下注射DF-Ex可以显著促进再上皮化、胶原沉积、皮肤细胞增殖、血管生成和抑制炎症，从而加速糖尿病皮肤创面的愈合。我们进一步探索了潜在的机制，发现DF-Ex通过激活Akt/β-catenin途径发挥积极作用。本研究表明DF-Ex可能为糖尿病皮肤创面愈合提供一种新的治疗策略。
Diabetic cutaneous wounds are one of the complications of diabetes mellitus (DM) and are difficult to cure at present. Autologous dermal fibroblasts (DFs) have shown great promise in skin regeneration and repair. However, whether exosomes derived from autologous dermal fibroblasts (DF-Ex) can be used to accelerate diabetic cutaneous wound healing is unclear. In this study, human umbilical vein endothelial cells (HUVECs) were treated with high glucose. We found that DF-Ex could reverse the damage produced by high glucose in HUVECs in vitro. A high-fat diet and streptozotocin were used to establish a rat model of type 2 diabetes mellitus (T2DM), and a diabetic cutaneous wound model was established in the T2DM rats. We discovered that subcutaneous injections of DF-Ex could significantly promote re-epithelialization, collagen deposition, skin cell proliferation, angiogenesis and inhibit inflammation to accelerate diabetic cutaneous wound healing. We further explored the underlying mechanism and found that DF-Ex exerted positive effects by activating the Akt/beta-catenin pathway. This research revealed that DF-Ex may provide a new treatment strategy for diabetic cutaneous wound healing.