尼古丁胺胺N-甲基转移酶调解了脂纤维细胞-肌纤维细胞过渡和抗灭的抵抗力
Mohammad Rehan1, Brian Deskin2, Ashish R Kurundkar3
1John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
The Journal of biological chemistry
|July 9, 2023
概括
尼古丁胺胺N-甲基转移酶 (NNMT) 在异常性肺纤维化 (IPF) 中被上调. 向NNMT可以通过将纤维细胞重新编程到再生状态来逆转纤维化.
科学领域:
- 细胞的新陈代谢
- 纤维化研究 纤维化研究
- 分子生物学分子生物学
背景情况:
- 代谢极大地影响细胞表型和命运.
- 尼古丁胺N-甲基转移酶 (NNMT) 涉及干细胞转换和瘤进展.
- 异形性肺纤维化 (IPF) 是一种慢性纤维化肺部疾病.
研究的目的:
- 调查NNMT在IPF中的作用.
- 确定NNMT对肺纤维细胞表型和细胞外基质生产的影响.
- 探索NNMT作为纤维性疾病治疗点的潜力.
主要方法:
- 在人类IPF肺部中量化NNMT表达.
- 在肺纤维细胞中评估NNMT的TGF-β1诱导.
- 利用NNMT沉默来评估对细胞外矩阵蛋白和纤维细胞表型的影响.
- 分析了NNMT对脂质转录因子 (TCF21,PPARγ) 和亡相关蛋白质 (Bim,PUMA) 的影响.
主要成果:
- 在IPF肺部,NNMT的表达很高,由TGF-β1.1诱导.
- 沉默NNMT会降低细胞外矩阵蛋白质的表达.
- NNMT促进了脂纤维细胞向亲纤维细胞肌纤维细胞的过渡.
- 尼诺基米降低了TCF21和PPARγ的调节,诱导了差异化的肌纤维细胞表型.
- 通过降低Bim和PUMA的调节,NNMT赋予了对肌纤维细胞的亡抵抗力.
结论:
- 在IPF中,NNMT在纤维细胞的新陈代谢重编程中起着关键作用,使其成为一种亲纤维细胞和抗亡的表型.
- 准NNMT可能提供一种策略,以促进像IPF这样的纤维性疾病的再生反应.
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