增加的乳酸生产通过稳定TGF-β1使PM2.5诱导的肺纤维化恶化
Zhihao Liu1, Wei Liu1, Huaiqing Wei2
1School of Public Health, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China.
Journal of advanced research
|August 4, 2025
概括
空气污染引发了肺巨细胞中乳酸的积累,通过抑制TGF-β1降解来促进肺纤维化. 降低乳酸水平可以缓解这种纤维性肺部疾病.
科学领域:
- 环境健康 环境健康
- 细胞生物学 细胞生物学
- 肺部医学 肺部医学
背景情况:
- 乳酸盐是糖解的副产物,与纤维化有关.
- 转化生长因子β1 (TGF-β1) 是纤维化发展的核心.
- 颗粒物 (PM2.5) 空气污染是肺纤维化的一个危险因素,但乳酸的作用尚不清楚.
研究的目的:
- 确定导致PM2.5诱导的肺纤维化中的乳酸积累的细胞.
- 在这种情况下,阐明乳酸如何影响TGF-β1.
主要方法:
- 光激活细胞分类,以隔离PM2.5暴露的小鼠的肺细胞.
- 免疫沉和免疫阻塞,以评估乳酸对TGF-β1稳定性的影响.
- 染色体免疫沉以研究组分激素乳化对Stub1基因表达的影响.
主要成果:
- 巨细胞在PM2.5诱导的肺纤维化中显示出乳酸生产增加.
- 乳酸抑制了Hsc70相互作用蛋白 (CHIP) 通过基因素乳化表达的碳酸末端.
- 减少CHIP损害了TGF-β1降解,增加了它的分泌和纤维化恶化.
结论:
- 由PM2.5诱导的巨细胞乳酸积累通过抑制CHIP来抑制TGF-β1无化和降解.
- 这导致TGF-β1分泌量增加和肺纤维化恶化.
- 抑制乳酸生产改善了小鼠的肺纤维化.
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