Department of Physiology and Psychology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province 730000, PR China.
Department of Orthopaedics, Lanzhou University First Affiliated Hospital, Lanzhou, Gansu Province 730000, PR China.
Environ Toxicol Pharmacol. 2020 Nov;80:103489. doi: 10.1016/j.etap.2020.103489. Epub 2020 Sep 7.
Numerous studies have reported that low-dose dimethyl sulfoxide (DMSO, <1.5%, v/v) can interfere with various cellular processes, such as cell proliferation, differentiation, apoptosis, and cycle. By contrast, minimal information is available about the effect of low-dose DMSO on cell migration. Here, we report the effect of DMSO (0.0005%-0.5%, v/v) on cellular migration in human normal hepatic L02 cells. We used the Cell Counting Kit-8 assay to measure cell viability, scratch wound healing assay to observe cellular migration, flow cytometry to analyze cell cycle and death pattern, reverse transcription quantitative polymerase chain reaction to evaluate mRNA expression, and Western blot to detect protein levels. After treatment with 0.0005% (v/v) DMSO, more cells entered S phase arrest, the MMP1/TIMP1 ratio increased, and HSP27 expression was elevated. After treatment with 0.1% (v/v) DMSO, more cells entered G0/G1 phase arrest, the MMP2/TIMP2 ratio increased, the p-p38 and p-Smad3 signaling pathways were activated, and neuropilin-1 expression was elevated. These results showed that cells migrate when their MMP1/TIMP1 and MMP2/TIMP2 ratios are imbalanced. Such migration is modulated by the p38/HSP27 signaling pathway and TGF-β/Smad3 dependent signaling pathway.
许多研究报告指出，低剂量二甲基亚砜（DMSO，<1.5%，v/v）可以干扰多种细胞过程，如细胞增殖、分化、凋亡和周期。相比之下，关于低剂量 DMSO 对细胞迁移的影响的信息很少。在这里，我们报告 DMSO（0.0005%-0.5%，v/v）对人正常肝 L02 细胞迁移的影响。我们使用细胞计数试剂盒-8 测定法来测量细胞活力，划痕愈合测定法来观察细胞迁移，流式细胞术来分析细胞周期和死亡模式，逆转录定量聚合酶链反应来评估 mRNA 表达，以及 Western blot 来检测蛋白质水平。用 0.0005%（v/v）DMSO 处理后，更多的细胞进入 S 期停滞，MMP1/TIMP1 比值增加，HSP27 表达升高。用 0.1%（v/v）DMSO 处理后，更多的细胞进入 G0/G1 期停滞，MMP2/TIMP2 比值增加，p-p38 和 p-Smad3 信号通路被激活，神经纤毛蛋白-1 表达升高。这些结果表明，当 MMP1/TIMP1 和 MMP2/TIMP2 比值失衡时，细胞会迁移。这种迁移受到 p38/HSP27 信号通路和 TGF-β/Smad3 依赖性信号通路的调节。
