线粒体叶酸通路调节肌纤维细胞分化和二氧化引起的肺纤维化
Yaqian Qu1,2, Ruonan Zhai1,3,4, Dandan Wang3,4
1Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Journal of translational medicine
|June 6, 2023
概括
线粒体叶酸代谢蛋白调节纤维细胞到肌纤维细胞的分化,这是二氧化诱导的肺纤维化 () 中的一个关键过程. 叶酸补充抑制了这一过程,并减少了小鼠的纤维化.
科学领域:
- 细胞生物学 细胞生物学
- 肺部医学 肺部医学
- 生物化学 生物化学
背景情况:
- 氧化诱导的肺纤维化 (氧化) 涉及到过度的细胞外基质沉积在肺组织中.
- 纤维细胞到肌纤维细胞的分化是病进展的关键驱动因素.
- 准肌纤维细胞分化是肺纤维化治疗的潜在治疗策略.
研究的目的:
- 研究线粒体叶酸代谢在肌纤维细胞分化中的作用.
- 探索针对线粒体叶酸酸治疗途径的潜力.
主要方法:
- 使用TGF-β在人肺纤维细胞中诱导的肌纤维细胞分化在体外.
- 在小鼠中诱导的肺纤维化,在体内使用暴露.
- 量化质谱法用于识别差异表达蛋白质.
主要成果:
- 线粒体叶酸通路中的蛋白质,包括MTHFD2和SLC25A32,在肌纤维细胞分化过程中被上调.
- 发现这些蛋白质可以负面调节肌纤维细胞分化.
- 在病患者和小鼠中观察到血叶酸水平的降低.
- 叶酸补充剂增加了MTHFD2和SLC25A32的表达,减少了氧化应激,并抑制了小鼠的肌纤维细胞分化和化.
结论:
- 线粒体叶酸通路在肌纤维细胞分化中起着调节作用.
- 这一途径代表了缓解二氧化诱导的肺纤维化的潜在治疗标.
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