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[病理性未成熟细胞的新型生物标志物——LR11可溶性形式]

[Novel biomarker for pathological immature cells--soluble form of LR11].

作者信息

Bujo Hideaki

机构信息

Department of Genome Research and Clinical Investigation, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.

出版信息

Rinsho Byori. 2012 May;60(5):469-76.

Abstract

LR11 (also called SorLA or SORL1), a member of the LDL receptor family, was originally discovered in 1996 from genes specifically expressed in the intimal smooth muscle cells of atherosclerotic plaques. The soluble form of LR11 (sLR11) as well as the membrane-bound form plays a key role in the phenotype conversion of medial smooth muscle cells into intimal smooth muscle cells through the activation of urokinase receptor/integrin-mediated intracellular pathways. The levels of sLR11 in serum or CSF are increased in patients with atherosclerotic diseases, Alzheimer's disease or malignant diseases including acute leukemias. The recently developed ELISA system using two specific antibodies against LR11 made it possible to measure sLR11 quantitatively and stably for many samples. Thus, a novel clinical examination is expected to detect the pathological immature cells important for the pathophysiology of the above diseases. The soluble receptor-based clinical approach, together with basic studies about the structure-function relationship, may shed light on the development of novel target therapy against pathological immature cells in the science fields of so far independently categorized diseases.

摘要

LR11(也称为SorLA或SORL1)是低密度脂蛋白受体家族的成员,最初于1996年从在动脉粥样硬化斑块内膜平滑肌细胞中特异性表达的基因中发现。LR11的可溶性形式(sLR11)以及膜结合形式通过激活尿激酶受体/整合素介导的细胞内途径,在中膜平滑肌细胞向内膜平滑肌细胞的表型转化中起关键作用。在患有动脉粥样硬化疾病、阿尔茨海默病或包括急性白血病在内的恶性疾病的患者中,血清或脑脊液中的sLR11水平会升高。最近开发的使用两种针对LR11的特异性抗体的ELISA系统,使得对许多样本进行sLR11的定量和稳定测量成为可能。因此,有望通过一种新型临床检查来检测对上述疾病病理生理学至关重要的病理性未成熟细胞。基于可溶性受体的临床方法,连同关于结构-功能关系的基础研究,可能会为迄今为止独立分类疾病的科学领域中针对病理性未成熟细胞的新型靶向治疗的开发提供线索。

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