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Low‐concentration DMSO accelerates skin wound healing by Akt / mTOR ‐mediated cell proliferation and migration in diabetic mice
Author(s) -
Guo Wei,
Qiu Wei,
Ao Xiang,
Li Weiqiang,
He Xiao,
Ao Luoquan,
Hu Xueting,
Li Zhan,
Zhu Ming,
Luo Donglin,
Xing Wei,
Xu Xiang
Publication year - 2020
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15052
Subject(s) - wound healing , pi3k/akt/mtor pathway , protein kinase b , fibroblast , cell growth , chemistry , cell migration , pharmacology , cancer research , microbiology and biotechnology , cell , medicine , signal transduction , immunology , biology , biochemistry , in vitro
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‐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.