Abstract:

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.

Key words: cellular senescence, janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3), bone marrow mesenchymal stem cells （BMSCs）, estrogen

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。

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

CLC Number: 

• R782