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收费相互作用蛋白抑制了小鼠肺纤维细胞中的转化生长因子β信号传递

Yu-Hua Chow^1,2, Cecilia López-Martínez^3,4,5, W Conrad Liles^2,6

¹Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine University of Washington Seattle Washington USA.

FASEB bioAdvances

|January 15, 2024

概括

收费相互作用蛋白 (TOLLIP) 缺乏会增强转化生长因子β (TGFβ) 在肺纤维细胞中的信号传递,导致细胞迁移和侵入的增加. 然而,Tollip淘汰赛小鼠显示肺损伤的解决能力受损,而不是纤维化增加.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
肺部医学肺部医学

背景情况:

众所周知,托尔相互作用蛋白 (TOLLIP) 能够调节先天免疫反应.
托利普的遗传变异与异常性肺纤维化风险和治疗反应有关.
托利普在器官纤维化,特别是肺纤维化中的作用尚不清楚.

研究的目的:

研究TOLLIP在转化增长因子β (TGFβ) 信号和肺纤维细胞反应中的作用.
确定TOLLIP在白血素诱导的肺纤维化小鼠模型中的作用.
测试TOLLIP缺乏会加剧TGFβ驱动的纤维化过程的假设.

主要方法:

来自野生型 (WT) 和托利普淘汰赛 (Tollip-/-) 小鼠的初级小鼠肺纤维细胞 (MLFs) 被TGFβ治疗.
使用RNA-seq和qPCR分析了转录变化.
功能性测试包括细胞迁移,增殖和入侵.
托利普-/-和WT小鼠接受了白胺诱导的肺损伤,评估了生存率,纤维化和炎症标志物.

主要成果:

与WT MLF相比,Tollip-/- MLF表现出增强的TGFβ诱导的基因表达,增加的迁移和更大的侵入性.
在Tollip-/-细胞和体内观察到通过SMAD2提升TGFβ信号的证据.
托利普/-小鼠的生存率降低,肺损伤的恢复受损,其特征是体重减轻和支气管支气管洗液蛋白质增加,但纤维化并没有增加.

结论:

托利普在肺纤维细胞中负面调节TGFβ信号,影响其功能反应.
虽然TOLLIP缺乏在体外促进了亲纤维细胞行为,但在体内不会加剧白血素诱导的肺纤维化.
托利普淘汰赛小鼠显示肺损伤的解决能力受损,这表明托利普在肺炎和修复中起着复杂的作用.

关键词:

在TGFβ中,TGFβ是TGFβ.郁金香:一个郁金香.有关收费的相互作用蛋白质.布莱莫辛 (Bleomycin) 是一种可怕的药物.纤维细胞的细胞.肺部受伤的原因是肺部受伤.肌纤维母细胞细胞.转化增长因子β转化增长因子β.

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