延迟关联酸迅速在基于翻译的积极反循环中对神经aminidase 3 进行升级
Sumeen Kaur Gill1, Richard H Gomer1
1Department of Biology, Texas A&M University, ILSB 301 Old Main Drive, College Station, TX 77843-3474, USA.
Cells
|March 14, 2026
概括
转化生长因子β-1 (TGF-β1) 快速增加神经氨基酶3 (NEU3) 的转化,创建一个积极的反循环,驱动纤维化. 抑制NEU3或其介质DDX3可以阻止这种纤维化过程.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 病理学 病理学 病理学
背景情况:
- 纤维化是一种病理性痕过程,由受伤愈合失调所驱动.
- 转化生长因子β-1 (TGF-β1) 是一种关键的细胞因子,与纤维化有关.
- 神经氨基酶3 (NEU3) 被TGF-β1上调并激活潜伏的TGF-β1,这表明一个反循环.
研究的目的:
- 为了研究TGF-β1在人类肺纤维细胞中的NEU3的快速调节.
- 阐明NEU3在涉及TGF-β1和延迟相关 (LAP) 的正反循环中的作用.
- 确定NEU3调节的分子媒介及其作为治疗点的潜力.
主要方法:
- 主要的人类肺纤维细胞被TGF-β1和LAP治疗.
- 评估了NEU3蛋白和mRNA水平,使用西式涂抹和RT-qPCR.
- 翻译和转录得到了评估.
- 研究了DEAD-box酶3 (DDX3) 和其抑制剂RK-33的作用.
主要成果:
- 通过增强翻译,TGF-β1在5分钟内迅速增加了细胞内和细胞外NEU3蛋白水平,独立于新的转录.
- 在LAP中,NEU3与TGF-β1.1进行了协同升级调节.
- NEU3抑制剂和DDX3抑制剂RK-33阻断了TGF-β1和LAP诱导的NEU3上调.
- TGF-β1,但不是LAP,诱导了DDX3的脱化.
结论:
- 一个快速的积极反循环涉及TGF-β1,LAP和NEU3,通过DDX3-依赖的翻译介导,有助于纤维化病原体.
- 准NEU3或DDX3可能为纤维化疾病提供治疗策略.
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