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  

Static Magnetic Field Promotes the Proliferation Activity and Migration Phenotype of Skin Fibroblasts through Activation of the FGFR1/JAK2/STAT3 Signaling Pathway

作　　者：张智慧[1] 马娟[1] 于扬[1] 余扬[1] 董祥林[1] ZHANG Zhihui;MA Juan;YU Yang(The First Affiliated Hospital of Xinjiang Medical University,Xinjiang Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院整形科,新疆乌鲁木齐830054

出　　处：《河北医学》2024年第5期750-756,共7页Hebei Medicine

基　　金：新疆维吾尔自治区自然科学基金资助项目,(编号:2022D01C368)。

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。Objective: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(3μmoL/L AG,3 nmoL/L LCK,and 20μmoL/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 sign

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 

分 类 号：R751[医药卫生—皮肤病学与性病学]