摘要
目的:探究非受体型蛋白酪氨酸激酶2/信号转导与转录激活子3(janus kinase 2/signal transducer and activator of transcription 3,JAK2/STAT3)信号通路在雌激素缺乏所致骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)衰老中的作用。方法:提取小鼠BMSCs,并用适宜浓度的过氧化氢(H2O2)诱导其衰老。进一步添加雌激素类似物17β-雌二醇(17β-estradiol,E2)或JAK通路抑制剂(鲁索替尼),用实时荧光定量聚合酶链反应(quantitative polymerase chain reaction,qPCR)、Western印迹法(Western blot)、β-半乳糖苷酶(SA-β-Gal)染色法检测其衰老指标及JAK2/STAT3信号通路的改变。结果:H2O2诱导的BMSCs衰老可被雌激素抑制,且伴随着JAK2/STAT3信号的下调,而进一步抑制JAK2/STAT3信号通路也可以挽救BMSCs的衰老。结论:JAK2/STAT3信号通路是雌激素调控BMSCs的衰老靶点,且抑制该通路可以挽救BMSCs的衰老。
Objective:To investigate the role of janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway in bone marrow mesenchymal stem cells(BMSCs)senescence caused by estrogen deficiency.Methods:BMSCs of mice were extracted and treated with H2O2 in appropriate concentration to be senescent.Estrogen analog 17β-estradiol(E2)or JAK pathway inhibitor(ruxolitinib)was further added,and senescence indicators and changes of JAK2/STAT3 signaling pathway were detected by quantitative polymerase chain reaction(qPCR),Western blot and SA-β-gal staining.Results:The senescence of BMSCs induced by H2O2 can be inhibited by estrogen and accompanied with the down-regulation of JAK2/STAT3 signaling.Further suppression of JAK2/STAT3 signaling pathway can also rescue BMSCs senescence.Conclusion:The JAK2/STAT3 signaling pathway is a target of estrogen-related BMSCs senescence,and inhibition of JAK2/STAT3 can rescue BMSCs senescence.
作者
武文婧
傅稼耀
魏玉
马鹏飞
吴珺华
WU Wenjing;FU Jiayao;WEI Yu;MA Pengfei;WU Junhua(Shanghai Engineering Research Center of Tooth Restoration and Regeneration,Department of Prosthodontics,School and Hospital of Stomatology,Tongji University,Shanghai 200072,China)
出处
《口腔颌面外科杂志》
CAS
2020年第5期288-294,共7页
Journal of Oral and Maxillofacial Surgery
基金
上海市自然科学基金项目(19ZR1462000)。
关键词
细胞衰老
酪氨酸激酶2/信号转导与转录激活子3
骨髓间充质干细胞
雌激素
cellular senescence
janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)
bone marrow mesenchymal stem cells(BMSCs)
estrogen