Department of Stem Cell & Regenerative Medicine.
Central Laboratory, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, P.R., China.
Br J Pharmacol. 2020 Jul;177(14):3327-3341. doi: 10.1111/bph.15052. Epub 2020 Apr 7.
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.
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.
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-β1 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.
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.
DMSO 已被发现可促进组织修复。然而，DMSO 在糖尿病皮肤伤口愈合中的作用及其潜在的分子机制尚不清楚。
通过 HE 染色、免疫组织化学和胶原染色，利用非糖尿病或糖尿病小鼠背部全层皮肤切除的伤口模型，评估 DMSO 对伤口愈合的影响。实时细胞分析和 5-乙炔基-2'-脱氧尿苷掺入试验用于研究 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。通过 Western blot 和抑制剂阻断鉴定相关信号通路。通过聚核糖体 mRNA 的 RT-qPCR 研究 DMSO 对下游靶基因翻译率的影响。
我们发现低浓度的 DMSO 通过促进非糖尿病和糖尿病小鼠成纤维细胞的增殖，显著加速皮肤伤口的闭合。此外，角质形成细胞迁移的增加也可能有助于加速伤口愈合，这是由成纤维细胞中 TGF-β1 分泌的增加所刺激的。此外，我们证明了 DMSO 的这种作用取决于 Akt/mTOR 介导的翻译控制以及一组与细胞增殖相关基因翻译的促进。不出所料，Akt/mTOR 信号通路的抑制剂 rapamycin 损害了 DMSO 诱导的伤口愈合和细胞增殖。
DMSO 可通过激活 Akt/mTOR 通路促进糖尿病小鼠皮肤伤口愈合。低浓度的 DMSO 为慢性皮肤伤口提供了一种替代药物，特别是对糖尿病患者。
