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内皮糖囊成分EMCN的损失导致淋巴细胞功能障碍

Zhengping Hu^1,2, Issahy Cano^1,2, Fengyang Lei^1,2

¹Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA (Z.H., I.C., F.L., J.L., H.G., E.I.P., M.S.-G., Y.S.E.N., P.A.D.).

Circulation research

|November 25, 2024

概括

在小鼠中,内素 (EMCN) 缺乏会导致损伤,包括白蛋白尿和细胞问题. 这凸显了EMCN在维护淋巴膜过屏障完整性和内皮细胞-细胞通信方面的关键作用.

科学领域:

腎臟病學 (nephrology) 是一種醫學專業.
分子生物学分子生物学
免疫学免疫学免疫学

背景情况:

末素 (EMCN) 是一种内皮特异性葡萄糖成分,在球体中高度表达.
EMCN具有抗炎作用,并调节血管内皮生长因子 (VEGF) 的活性.
全球首个EMCN淘汰赛小鼠模型被用于研究EMCN缺陷效应.

研究的目的:

调查全球EMCN缺陷的表型和功能后果.
阐明EMCN在维持质细胞结构和功能的作用.

主要方法:

全球EMCN淘汰赛小鼠 (EMCN-/-) 的生成.
通过流细胞计对脏髓状细胞透的分析.
使用传输电子显微镜评估膜过屏障超结构.
测量尿中的白蛋白,肌和总蛋白质.
对于EMCN,白蛋白和podocin的免疫组织化学.
质内皮细胞和细胞的RNA测序.
西方斑点分析用于蛋白质定量.

主要成果:

在EMCN-/-小鼠中,CD45+骨髓细胞透和VCAM-1表达增加.
在EMCN-/-小鼠中观察到白膜尿和球细胞脚过程的消失.
RNA测序揭示了细胞对细胞粘附的改变,MAPK/ERK信号传递和VEGF信号传递途径.
在EMCN-/-小鼠中检测到可多辛mRNA和蛋白质水平的显著下调.

结论:

EMCN对于维持正常的膜过屏障结构和功能至关重要.
支持质内皮紧密结合的完整性和恒常性.
通过内皮细胞-细胞交叉声,EMCN会影响细胞功能.

关键词:

它们的内皮质 (endothelium).球膜过障碍物球膜过障碍物葡萄糖糖的性糖质 (glycocalyx) 是一种这是一种炎症炎症炎症炎症.鼠标鼠标鼠标鼠标葡萄细胞 (podocytes) 是一种细胞.

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