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巨细胞OTUD1-CARD9轴驱动异二醇诱导的炎症性心脏重塑

Jinfu Qian^1,2, Qinyan Wang², Jiachen Xu¹

¹Department of Cardiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Clinical and translational medicine

|August 9, 2024

概括

卵巢瘤二维基因酶1 (OTUD1) - 酶相关招募域9 (CARD9) 轴促进异二醇诱导的心力衰竭的炎症. 准这个轴可以保护心脏免受损伤.

科学领域:

免疫学免疫学免疫学
心血管生物学心血管生物学
分子生物学分子生物学

背景情况:

慢性炎症驱动因异二醇 (ISO) 引起的心力衰竭 (HF).
与酶相关的招募域 (CARD) 蛋白质是先天性免疫炎症的关键.
卡片在ISO驱动的心脏改造中的作用还没有得到充分研究.

研究的目的:

研究CARD9在ISO诱导的心脏炎症和重塑中的作用.
为了阐明在这个过程中将OTUD1和CARD9联系在一起的分子机制.

主要方法:

使用 Card9 淘汰赛小鼠和复制骨髓模拟小鼠.
在初级巨细胞,心肌细胞,纤维细胞和HEK-293T细胞中进行了机制研究.
在ISO管理后评估心脏炎症,重塑和功能障碍.

主要成果:

在ISO注入的小鼠心脏中,CARD9的调节升高.
全身或骨髓细胞特异性的CARD9缺陷抑制了ISO诱导的心脏炎症和重塑.
OTUD1通过去除与K33结合的无素来增强CARD9的活性,促进CBM复合体的组装和NF-κB的激活.
骨髓特异性OTUD1缺失减轻了ISO诱导的心脏炎症和重塑.

结论:

OTUD1-CARD9轴是ISO挑战性巨细胞中一种新的促炎途径.
针对OTUD1-CARD9轴提供了针对ISO诱导心力衰竭的保护策略.

关键词:

卡片9 卡片9 是一个卡片.在OTUD1中,我们可以使用OTUD1.心脏衰竭是因为心脏衰竭.这是一种炎症炎症炎症炎症.这是一种异蛋白醇 (isoproterenol).巨细胞是一个巨细胞.

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