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TET1 调节表达和人类气道平滑肌肉的扩散
Ruping Wang1, Guoning Liao1, Dale D Tang1
1Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York.
十一转位甲基细胞二氧化酶1 (TET1) 在喘中促进呼吸道光滑肌肉的扩散. 抑制TET1通过影响nestin-mTOR通路来减少这种扩散,从而提供了一个潜在的治疗标.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 肺部病理学 肺部病理学
背景情况:
- 喘涉及异常的呼吸道光滑肌肉 (ASM) 扩散,使呼吸道壁变厚,阻塞情况恶化.
- 导致ASM在喘中扩散的确切机制尚不清楚.
- 十一种转位甲基细胞二氧化酶 (TET) 酶通过将5-甲基细胞因转化为5-基甲基细胞因来调节DNA甲基化,从而影响基因表达.
研究的目的:
- 研究TET酶,特别是TET1在调节喘中ASM增殖中的作用.
- 探索TET1影响ASM细胞生长的分子机制.
主要方法:
- 在人类喘ASM细胞中评估了TET1活性和蛋白质水平.
- 在喘和非喘ASM细胞中测量了5-基甲基细胞素水平.
- 利用TET1敲除 (KD) 来评估其对5-基甲基细胞素,内斯表达和mTOR通路的影响.
- 研究了TET1抑制对血小板衍生的生生长因子诱导的信号传递和ASM细胞增殖的影响.
主要成果:
- 在喘性ASM细胞中,TET1活性和蛋白质升高,与更高的5-氧甲基细胞蛋白度相关.
- TET1 KD,但不是TET2 KD,降低了喘细胞中的5-基甲基细胞素水平.
- TET1 KD降低了内斯的表达,并抑制了mTOR通路 (包括p70S6K,4E-BP,S6和Akt的酸化).
- 抑制TET1减弱的ASM细胞增殖.
结论:
- TET1在驱动喘中ASM扩散方面发挥着重要作用.
- 通过TET1介导的增殖似乎是通过nestin-mTOR信号轴发生的.
- TET1代表了管理喘相关气道改造的潜在治疗标.
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