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首页> 外文期刊>Neurosurgery >KRIT1/cerebral cavernous malformation 1 protein localizes to vascular endothelium, astrocytes, and pyramidal cells of the adult human cerebral cortex.
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KRIT1/cerebral cavernous malformation 1 protein localizes to vascular endothelium, astrocytes, and pyramidal cells of the adult human cerebral cortex.

机译：KRIT1 /脑海绵状畸形1蛋白位于成人大脑皮层的血管内皮，星形胶质细胞和锥体细胞中。

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OBJECTIVE: Mutations in KRIT1 cause familial cerebral cavernous malformation, an autosomal dominant disorder affecting primarily the central nervous system vasculature. Although recent studies have suggested that Krev-1 interaction trapped 1 (KRIT1) is a microtubule-associated protein that interacts with integrin cytoplasmic domain-associated protein-1alpha, the function of KRIT1 remains elusive. METHODS: We used Western blotting and immunohistochemistry with specific KRIT1 polyclonal antibodies to investigate KRIT1 protein expression in diverse cerebral and extracerebral tissues. RESULTS: Immunostaining demonstrates that although KRIT1 is expressed in a broad variety of human organs, it localizes to the vascular endothelium of each, specifically to capillaries and arterioles. KRIT1 antibody fails to stain fenestrated capillaries in the kidney, the liver, or the red pulp of the spleen, where endothelial cells do not to adhere to one another. In contrast, intense staining is observed in the thymus and the white pulp of the spleen, where specialized blood-organ barriers are formed. Other cell types, including various epithelia, cardiac myocytes, and hepatocytes, also stain with KRIT1. CONCLUSION: Although KRIT1 expression is seen in every endothelium studied, cerebral cavernous malformation lesions are seen almost exclusively in the central nervous system, suggesting that additional cell type(s) contribute to the pathophysiology of cerebral cavernous malformations. Here, we demonstrate that KRIT1 is also present in cells and structures integral to the cerebral angiogenesis and formation of the blood-brain barrier, namely, endothelial cells and astrocytic foot processes, as well as pyramidal neurons in the cerebral cortex.
机译：目的：KRIT1突变会导致家族性脑海绵状畸形，这是一种常染色体显性遗传疾病，主要影响中枢神经系统脉管系统。尽管最近的研究表明，Krev-1相互作用捕获1（KRIT1）是一种与整管蛋白胞质域相关蛋白1alpha相互作用的微管相关蛋白，但KRIT1的功能仍然难以捉摸。方法：我们使用Western印迹和免疫组化与特定的KRIT1多克隆抗体来研究KRIT1蛋白在各种脑和脑外组织中的表达。结果：免疫染色表明，尽管KRIT1在多种人体器官中表达，但它定位于每个器官的血管内皮，特别是毛细血管和小动脉。 KRIT1抗体无法染色肾脏，肝脏或脾脏的红色浆液中的有孔的毛细血管，在这些毛细血管中内皮细胞不会相互粘附。相反，在胸腺和脾脏的白色牙髓中观察到强烈的染色，在那里形成了专门的血器官屏障。其他细胞类型，包括各种上皮细胞，心肌细胞和肝细胞，也被KRIT1染色。结论：尽管在每个研究的内皮细胞中均可见KRIT1表达，但脑海绵状畸形病变几乎仅在中枢神经系统中可见，这表明其他细胞类型有助于脑海绵状畸形的病理生理。在这里，我们证明KRIT1也存在于大脑血管生成和血脑屏障形成所必需的细胞和结构中，即内皮细胞和星形胶质细胞足突以及大脑皮质中的锥体神经元。

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