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UCHL1通过Sphingosine Kinase-1调节辐射肺损伤

Yulia Epshtein¹, Biji Mathew¹, Weiguo Chen¹

¹Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, Chicago, IL 60612, USA.

|October 13, 2023

概括

UCHL1二基化SphK1,影响脂信号传递和辐射诱导肺损伤 (RILI) 的严重程度. 抑制UCHL1会使RILI恶化,这表明UCHL1调制是肺损伤的治疗策略.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
肺部医学肺部医学

背景情况:

由于改变Akt和UCHL1水平,GADD45a缺乏会增加对辐射引起的肺损伤 (RILI) 的敏感性.
脊髓脂质在RILI中发挥作用,SphK1缺乏增加了易感性.
UCHL1 (ubiquitin c-terminal hydrolase L1) 是一种参与细胞应激反应的双化酶.

研究的目的:

调查假设UCHL1介导的SphK1无化调节是RILI中的关键机制.
探索UCHL1在与辐射损伤相关的脂信号通路中的作用.

主要方法:

对人类肺内皮细胞 (EC) 的辐射和UCHL1和SphK1表达的评估.
免疫沉和西部斑点检测SphK1无处不在.
使用UCHL1siRNA和抑制剂LDN-5744来评估UCHL1在SphK1无化和EC屏障功能的作用.
在用LDN-5744.4预先治疗的小鼠中评估RILI的严重程度.

主要成果:

在人类肺部EC中,辐射上调了UCHL1和SphK1.
辐射在EC中增加了SphK1的泛化,但通过抑制UCHL1 (siRNA或LDN-5744) 减少了这种SphK1泛化.
抑制UCHL1减弱了脂介导的EC屏障增强,并显著增加了小鼠RILI严重性.

结论:

在暴露于辐射后,UCHL1调节SphK1的无处不在和表达.
通过UCHL1调节脂体信号传递是RILI的一个关键因素.
调节UCHL1活动为RILI提供了潜在的治疗策略.

关键词:

在UCHL1上.辐射肺部损伤是什么意思斯芬戈氨酸激酶 1 的作用.

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