Low-concentration DMSO accelerates skin wound healing by Akt/mTOR-mediated cell proliferation and migration in diabetic mice
Low-concentration DMSO accelerates skin wound healing by Akt/mTOR-mediated cell proliferation and migration in diabetic mice
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低浓度 DMSO 通过 AKT/mTOR 介导的糖尿病小鼠细胞增殖和迁移加速皮肤伤口愈合
DOI：
10.1111/bph.15052
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发表时间：
2020-04-07
影响因子：
7.3
通讯作者：
Xu, Xiang
中科院分区：
文献类型：
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作者：
Guo, Wei;Qiu, Wei;Xu, Xiang
研究背景和目的DMSO具有促进组织修复的作用。然而，DMSO在糖尿病皮肤伤口愈合中的作用和潜在的分子机制仍不清楚。实验方法DMSO对伤口愈合的影响通过HE染色，免疫组织化学和胶原蛋白染色使用非糖尿病或糖尿病小鼠背部全层皮肤切除的伤口模型进行评价。采用实时细胞分析和5-乙炔基-2 '-脱氧尿苷掺入试验来研究DMSO对原代成纤维细胞增殖的影响。transwell试验用于研究角质形成细胞迁移。相关的信号通路通过蛋白质印迹和抑制剂阻断来鉴定。DMSO对下游靶基因的翻译速率的影响进行了研究，通过RT-qPCR的多聚核糖体mRNA.Key结果我们发现，低浓度的DMSO显着加速皮肤伤口愈合，促进成纤维细胞增殖在非糖尿病和糖尿病小鼠。此外，角质形成细胞的迁移增加也可能有助于加速伤口愈合，这是由成纤维细胞分泌增加的TGF-β 1刺激的。此外，我们证明了DMSO的这种作用依赖于Akt/mTOR介导的翻译控制和促进一组细胞增殖相关基因的翻译。正如预期的那样，DMSO诱导的伤口愈合和细胞增殖受损的雷帕霉素，Akt/mTOR signaling.Conclusion和Implications抑制剂DMSO可以通过激活Akt/mTOR通路促进糖尿病小鼠皮肤伤口愈合。低浓度DMSO为慢性皮肤伤口，特别是糖尿病患者提供了一种替代药物。
Background and Purpose DMSO has been found to promote tissue repair. However, the role of DMSO in diabetic skin wound healing and the underlying molecular mechanisms are still unclear.Experimental Approach The effects of DMSO on wound healing were evaluated by HE staining, immunohistochemistry and collagen staining using a wound model of full-thickness skin resection on the backs of non-diabetic or diabetic mice. Real-time cell analysis and 5-ethynyl-2 '-deoxyuridine incorporation assays were used to study the effect of DMSO on primary fibroblast proliferation. A transwell assay was used to investigate keratinocyte migration. The associated signalling pathway was identified by western blotting and inhibitor blocking. The effect of DMSO on the translation rate of downstream target genes was studied by RT-qPCR of polyribosome mRNA.Key Results We found that low-concentration DMSO significantly accelerated skin wound closure by promoting fibroblast proliferation in both nondiabetic and diabetic mice. In addition, increased migration of keratinocytes may also contribute to accelerated wound healing, which was stimulated by increased TGF-beta 1 secretion from fibroblasts. Furthermore, we demonstrated that this effect of DMSO depends on Akt/mTOR-mediated translational control and the promotion of the translation of a set of cell proliferation-related genes. As expected, DMSO-induced wound healing and cell proliferation were impaired by rapamycin, an inhibitor of Akt/mTOR signalling.Conclusion and Implications DMSO can promote skin wound healing in diabetic mice by activating the Akt/mTOR pathway. Low-concentration DMSO presents an alternative medication for chronic cutaneous wounds, especially for diabetic patients.