介质细胞干细胞通过重编程胸膜上皮细胞的DNA甲基化来逆转胸膜衰老
Zailing Yang1,2, Chuan Tian1, Zhixu He3
1The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China.
介酶干细胞 (MSCs) 通过调节DNA甲基化,使老年肌肉恢复青春. MSCs通过降低NGF等转录因子的甲基化,上调KRT17和FOXJ1.1,促进胸膜上皮细胞 (TEC) 增殖.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 老年学是一门学科.
背景情况:
- 胸膜退化,标志着胸膜上皮细胞 (TEC) 数量和活性减少,有助于衰老.
- 介质细胞干细胞 (MSCs) 提供了一个有前途的治疗策略,用于胸膜衰老.
- 在TEC中MSC治疗的基础上,精确的DNA甲基化机制在很大程度上仍未被探索.
研究的目的:
- 研究MSCs对老年 rhesus的胸膜结构和功能的影响.
- 阐明DNA甲基化修饰在MSC介导的老年胸膜上皮细胞复原中的作用.
- 为了确定关键的基因和调节途径参与MSC治疗胸膜衰老.
主要方法:
- 在接受MSCs治疗的老年 rhesus中建立了胸膜衰老模型.
- 使用血素-氨酸染色,免疫光学和ELISA评估胸膜结构和功能.
- 在与MSCs共同培养的TEC衰老模型中分析DNA甲基化和转录组变化.
- 转录因子甲基化和mRNA表达之间的相关性分析,通过q-PCR,免疫光学和西方斑点验证.
主要成果:
- MSCs改善了老的胸膜结构和功能,减少衰老标志物 (β-Gal,P16,P21) 和增强TEC活动.
- 观察到差异性DNA甲基化:在MSC治疗组中,501个基因显示促进体甲基化增加,591个基因显示促进体甲基化减少.
- 具体来说,像NGF这样的转录因子的甲基化减少与KRT17和FOXJ1的上调相关,促进TEC的增殖和生长.
结论:
- 通过调节DNA甲基化概况,MSCs有效地使衰老的胸腺复发.
- 治疗效果涉及下调特定转录因子的甲基化,如NGF.
- 这种表观遗传重编程通过KRT17和FOXJ1等关键基因的上调促进TEC的增殖,恢复胸膜功能.
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