Low‐concentration DMSO accelerates skin wound healing by Akt/mTOR‐mediated cell proliferation and migration in diabetic mice
- 13 March 2020
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 177 (14), 3327-3341
- https://doi.org/10.1111/bph.15052
Abstract
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 nondiabetic 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‐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. 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.Funding Information
- National Natural Science Foundation of China (cstc2015jcyjA10078)
- Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission (81571913, 81871568)
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