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河北医学  2024, Vol. 30 Issue (5): 750-755    DOI: 10.3969/j.issn.1006-6233.2024.05.09
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静态磁场通过激活FGFR1/JAK2/STAT3信号通路促进皮肤成纤维细胞的增殖活性和迁移表型
张智慧, 马娟, 于扬, 余扬, 董祥林
新疆医科大学第一附属医院整形科, 新疆 乌鲁木齐 830054
Static Magnetic Field Promotes the Proliferation Activity and Migration Phenotype of Skin Fibroblasts through Activation of the FGFR1/JAK2/STAT3 Signaling Pathway
ZHANG Zhihui, MA Juan, YU Yang, et al
The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Urumqi 830054, China
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摘要 目的: 通过体外实验探讨静态磁场(SMF)对皮肤成纤维细胞增殖活性和迁移表型的调控作用与潜在机制。方法: 将人皮肤成纤维细胞(HSFs)分为5组,包括对照组、SMF组、SMF+阿魏酸组、SMF+芦可替尼组、SMF+Stattic组。对照组为正常培养的HSFs;SMF组的HSFs细胞暴露于1mT的SMF中。其余三组分别将FGFR1、JAK2、STAT3的抑制剂(3μmoL/L阿魏酸、3nmoL/L芦可替尼、20μmoL/L的Stattic)与HSFs一起预培养,并暴露于1mT的SMF中,所有组均处理24h。用细胞计数试剂盒-8(CCK-8)分析细胞的增殖活性。用ELISA试剂盒法检测人类B细胞淋巴瘤2相关X蛋白(BAX)的水平。用Western blot检测凋亡标志蛋白cleaved-caspase3及FGFR1、JAK2、STAT3、磷酸化的(p)-FGFR1、p-JAK2、p-STAT3的表达以及细胞迁移相关表型高迁移率组蛋白1(HMGB1)、波形蛋白(vimentin)、血管内皮生长因子A(VEGFA)、基质金属蛋白酶-9(MMP-9)、MMP-2的表达。结果: 与对照组比,SMF组的细胞增殖活性增加,BAX的水平减少,cleaved-caspase3的蛋白表达水平下调,p-FGFR1、p-JAK2、p-STAT3、HMGB1、vimentin、VEGFA、MMP-9、MMP-2的表达水平均显著上调(均P<0.05)。与SMF组比,SMF+阿魏酸组的细胞增殖活性降低,BAX的水平增加,cleaved-caspase3的蛋白表达水平上调,而p-FGFR1、p-JAK2、p-STAT3、HMGB1、vimentin、VEGFA、MMP-9、MMP-2的表达均显著下调(均P<0.05)。与SMF组比,SMF+芦可替尼组的细胞增殖活性降低,BAX的水平增加,cleaved-caspase3的蛋白表达水平上调,JAK2、p-JAK2、p-STAT3、HMGB1、vimentin、VEGFA、MMP-9、MMP-2的表达水平均显著下调(均P<0.05)。与SMF组比,SMF+Stattic组的细胞增殖活性降低,BAX的水平增加,cleaved-caspase3的蛋白表达水平上调,STAT3、p-STAT3、HMGB1、vimentin、VEGFA、MMP-9、MMP-2的表达水平均显著下调(均P<0.05)。结论: SMF通过激活FGFR1/JAK2/STAT3信号通路促进皮肤成纤维细胞的增殖活性和迁移表型。
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关键词 静态磁场皮肤成纤维细胞FGFR1/JAK2/STAT3信号通路增 殖迁 移    
AbstractObjective: To investigate the regulatory effects of static magnetic field (SMF) on the proliferation activity and migration phenotype of skin fibroblasts and its potential mechanism. Methods: Human skin fibroblasts (HSFs) were divided into five groups: control group, SMF group, SMF+AG group, SMF+LCK group, and SMF+Stattic group. The control group was HSFs cultured normally. HSFs cells in the SMF group were exposed to 1mT SMF. The other three groups were pre-incubated with inhibitors of FGFR1, JAK2, and STAT3 (3 μmoL/L AG, 3 nmoL/L LCK, and 20 μmoL/L Stattic) together with HSFs and exposed to 1 mT SMF. All groups were treated for 24 hours. Cell Counting Kit-8 (CCK-8) was used to analyze cell proliferation activity. ELISA was used to detect the level of Bcl-2-associated X protein (BAX). Western blot was used to detect the expression of apoptotic marker cleaved-caspase3 and FGFR1, JAK2, STAT3, phosphorylated (p)-FGFR1, p-JAK2, p-STAT3, and the expression of cell migration-related phenotypes high-mobility group box 1 (HMGB1), vimentin, vascular endothelial growth factor A (VEGFA), matrix metallopeptidase-9 (MMP-9), and MMP-2. Results: Compared with the control group, the cell proliferation activity in the SMF group was increased, the BAX level was decreased, the protein expression level of cleaved-caspase3 was down-regulated, and the expression levels of p-FGFR1, p-JAK2, p-STAT3, HMGB1, vimentin, VEGFA, MMP-9, and MMP-2 were all significantly up-regulated (all P<0.05). Compared with the SMF group, the cell proliferation activity in the SMF+AG group was decreased, the BAX level was increased, the protein expression level of cleaved-caspase3 was up-regulated, and the expression levels of p-FGFR1, p-JAK2, p-STAT3, HMGB1, vimentin, VEGFA, MMP-9, and MMP-2 were all significantly down-regulated (all P<0.05). Compared with the SMF group, the cell proliferation activity in the SMF+LCK group was decreased, the BAX level was increased, the protein expression level of cleaved-caspase3 was up-regulated, and the expression levels of JAK2, p-JAK2, p-STAT3, HMGB1, vimentin, VEGFA, MMP-9, and MMP-2 were all significantly down-regulated (all P<0.05). Compared with the SMF group, the cell proliferation activity in the SMF+Stattic group was decreased, the BAX level was increased, the protein expression level of cleaved-caspase3 was up-regulated, and the expression levels of STAT3, p-STAT3, HMGB1, vimentin, VEGFA, MMP-9, and MMP-2 were all significantly down-regulated (all P<0.05). Conclusion: SMF promotes the proliferation activity and migration phenotype of skin fibroblasts by activating the FGFR1/JAK2/STAT3 signaling pathway.
Key wordsStatic magnetic field    Skin fibroblasts    FGFR1/JAK2/STAT3 signaling pathway    Proliferation    Migration
    
基金资助:新疆维吾尔自治区自然科学基金资助项目,(编号:2022D01C368)
通讯作者: 董祥林   
引用本文:   
张智慧, 马娟, 于扬, 余扬, 董祥林. 静态磁场通过激活FGFR1/JAK2/STAT3信号通路促进皮肤成纤维细胞的增殖活性和迁移表型[J]. 河北医学, 2024, 30(5): 750-755.
ZHANG Zhihui, MA Juan, YU Yang, et al. Static Magnetic Field Promotes the Proliferation Activity and Migration Phenotype of Skin Fibroblasts through Activation of the FGFR1/JAK2/STAT3 Signaling Pathway. HeBei Med, 2024, 30(5): 750-755.
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