Promoting effect of ultra-low dose DMSO on fibroblast proliferation and its underlying mechanism

TAN Ranjing; KANG Tehao; WU Dengyan

doi:10.16016/j.2097-0927.202507107

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Promoting effect of ultra-low dose DMSO on fibroblast proliferation and its underlying mechanism

Basic Medicine | 更新时间：2025-10-13

- Promoting effect of ultra-low dose DMSO on fibroblast proliferation and its underlying mechanism
- Journal of Army Medical University Vol. 47, Issue 19, Pages: 2385-2395(2025)
- 作者机构：
  
  1.重庆医科大学附属第二医院皮肤与医疗美容中心，重庆
  2.重庆巫山县人民医院皮肤美容整形科，重庆
- 作者简介：
- 基金信息：
  
  the General Project of Natural Science Foundation of Chongqing(CSTB2023NSCQ-MSX0410;CSTB2023NSCQ-MSX0230)
- DOI：10.16016/j.2097-0927.202507107
  CLC： R322.99;R329.28;R914.4
- Received：16 April 2025，
  
  Revised：2025-06-05，
  
  Published：15 October 2025
- 稿件说明：
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谭燃景，康特豪，吴登艳.超低浓度二甲基亚砜促进皮肤成纤维细胞增殖作用及机制研究［J］.陆军军医大学学报，2025，47（19）：2385-2395.DOI：10.16016/j.2097-0927.202507107.

TAN R J，KANG T H，WU D Y.Promoting effect of ultra-low dose DMSO on fibroblast proliferation and its underlying mechanism［J］.J Army Med Univ，2025，47（19）：2385-2395.DOI：10.16016/j.2097-0927.202507107.
谭燃景，康特豪，吴登艳.超低浓度二甲基亚砜促进皮肤成纤维细胞增殖作用及机制研究［J］.陆军军医大学学报，2025，47（19）：2385-2395.DOI：10.16016/j.2097-0927.202507107. DOI：

TAN R J，KANG T H，WU D Y.Promoting effect of ultra-low dose DMSO on fibroblast proliferation and its underlying mechanism［J］.J Army Med Univ，2025，47（19）：2385-2395.DOI：10.16016/j.2097-0927.202507107. DOI：

摘要

目的

探讨超低浓度二甲基亚砜（Dimethyl sulfoxide，DMSO）对小鼠皮肤成纤维细胞增殖的影响及其分子机制。

方法

采用四甲基偶氮唑蓝（methylthiazolyldiphenyl-tetrazolium bromide，MTT）检测不同浓度的DMSO对皮肤成纤维细胞增殖活性的影响；用双荧光素酶检测系统检测细胞中的复合物帽状依赖翻译蛋白活性的影响；用7-甲基鸟苷三磷酸（7-methylguanosine triphosphate，

mGTP）下拉实验及Western blot检测DMSO处理后细胞的真核起始因子4E蛋白（eukaryotic translation initiation factor 4E，eIF4E）及其结合蛋白真核翻译起始因子4E结合蛋白1（eukaryotic translation initiation factor 4E-binding protein 1，4E-BP1）、真核翻译起始支架蛋白（eukaryotic translation initiation factor ，eIF4G）的变化；用哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin， mTOR）的抑制剂雷帕霉素干预后，Western blot检测PI3K/Akt/mTOR信号通路蛋白的量及其磷酸化水平的改变。

结果

11.0 nmol/L DMSO不仅可显著提高细胞的增殖率（

0.05），还能提高细胞帽状依赖翻译起始荧光素酶报告基因活性（

0.05）；

mGTP下拉实验及Western blot检测结果显示，11.0 nmol/L DMSO处理细胞后，可显著抑制4E-BP1与eIF4E的结合（

0.05），明显促进eIF4G与eIF4E的结合（

0.05）；p-Akt（S473）、p-mTOR（S2448）、p-4E-BP1（T37/46）、p-p70S6k（T421/424）的磷酸化水平与对照组比较明显上调（

0.05）；AKt、mTOR、 p70S6K、S6、eIF4E、4E-BP1 总蛋白表达均上调；与对照组相比，雷帕霉素干预组， p-Akt（S473）、p-mTOR（S2448）、p-p70S6K （T421/424））、p-S6（S235/236）的磷酸化水平下调（

0.05）；雷帕霉素加DMSO组与雷帕霉素组的磷酸化水平比较，除p-eIF4E（S209）外，均明显上调（

0.05）；对Akt、mTOR、p70S6k、4E-BP1蛋白表达的研究发现，与对照组相比， DMSO组除4E-BP1外，Akt、p70S6K、mTOR蛋白表达均呈上调趋势（

0.05）雷帕霉素组均明显下调

（P

0.05）；DMSO加雷帕霉素组与雷帕霉素组的表达相比，除p70S6K外，均明显上调（

0.05）。

结论

超低浓度的DMSO（11.0 nmol/L）可通过介导PI3K/Akt/mTOR信号通路来促进小鼠皮肤成纤维细胞的增殖，从而加速创面愈合。

Abstract

Objective

To investigate the effect of ultra-low dose of dimethyl sulfoxide (DMSO) on the proliferation of skin fibroblasts and to explore its underlying molecular mechanism.

Methods

MTT assay was used to determine the effect of different concentrations of DMSO on the proliferation of skin fibroblasts. Pull-down assay with 7-methylguanosine triphosphate (

mGTP) and Western blotting was employed to detect the changes in eukaryotic initiation factor 4E (eIF4E) and its binding protein

4E-BP1

and eukaryotic translation initiation factor 4G (eIF4G). After intervention with mTOR inhibitor

rapamycin

the alterations in the expression and phosphorylation levels of proteins within the PI3K/Akt/mTOR signaling pathway were examined with Western blotting.

Results

Treatment with 11.0 nmol/L DMSO significantly increased both the cell proliferation rate (

0.05) and the activity of the cap-dependent translation initiation luciferase reporter gene (

0.05). Results from 7mGTP pull-down assay and Western blotting demonstrated that 11.0 nmol/L DMSO notably inhibited the binding of 4E-BP1 to eIF4E (

0.05) while promoting the binding of eIF4G to eIF4E (

0.05). Compared with the control group

the phosphorylation levels of p-Akt (S473)

p-mTOR (S2448)

p-4E-BP1 (T37/46)

and p-p70S6K (T421/424) were upregulated (

0.05); the total protein expressions of Akt

mTOR

p70S6K

eIF4E

and 4E-BP1 were increased to varying degrees(

0.05). In the RAPA intervention group

the phosphorylation levels of p-Akt (S473)

p-mTOR (S2448)

p-p70S6K (T421/424)

and p-S6 (S235/236) were significantly lower than those in the control group (

0.05). When comparing the RA + DMSO group with the RA group

the phosphorylation levels of all aforementioned proteins were significantly upregulated except for p-eIF4E (S209) (

0.05). For protein expression analysis: relative to the control group

the DMSO gro

up exhibited increased expressions of Akt

p70S6K

and mTOR (

0.05) except for 4E-BP1; the RAPA group showed significant downregulation in all these proteins (

0.05); compared with the RA group

the RA + DMSO group displayed significantly higher expressions of all these proteins except for p70S6K (

0.05).

Conclusion

Ultra-low dose of DMSO (11.0 nmol/L) promotes the proliferation of mouse skin fibroblasts by mediating the PI3K/Akt/mTOR signaling pathway

thereby potentially accelerating wound healing.

关键词

Keywords

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