Megalin is an endocytic receptor in the proximal tubules that reabsorbs filtered proteins in the kidneys. Recycling of megalin after endocytosis and its expression on the apical plasma membrane of the proximal tubule are critical for its function. The expression of megalin in the kidney undergoes dynamic changes under physiologic and pathophysiologic conditions. Receptors and various effector signaling components regulate megalin expression and, potentially, function. Genetic manipulation and rare mutations in megalin suggest that a lack of or deficiency in megalin expression/function promotes tubular proteinuria and albuminuria. However, the role of megalin in kidney diseases associated with obesity, diabetes, hypertension, and nephrotoxicity remains unclear. To address these questions, animal and human studies have indicated megalin as a protective, injurious, and potentially urinary marker of nephropathy. This article reviews the literature on the regulation of megalin expression and the role of megalin in the pathophysiology of the kidney under experimental and clinical conditions. Moreover, this review articulates the need for studies that can clarify whether megalin can serve as a therapeutic target, in one way or the other, to treat kidney disease.

中文翻译：

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Megalin：肾脏的伙伴还是克星？


Megalin 是近端小管中的一种内吞受体，可重吸收肾脏中过滤的蛋白质。内吞作用后 megalin 的再循环及其在近端小管顶端质膜上的表达对其功能至关重要。Megalin 在肾脏中的表达在生理和病理生理条件下发生动态变化。受体和各种效应子信号转导组分调节 megalin 表达，并可能调节功能。Megalin 的基因操作和罕见突变表明，Megalin 表达/功能的缺乏或缺乏会促进肾小管蛋白尿和白蛋白尿。然而，megalin 在与肥胖、糖尿病、高血压和肾毒性相关的肾脏疾病中的作用仍不清楚。为了回答这些问题，动物和人类研究表明 megalin 是一种保护性、有害性和潜在的肾病尿液标志物。本文综述了实验和临床条件下 megalin 表达调控以及 megalin 在肾脏病理生理学中的作用的文献。此外，本综述阐明了研究的必要性，这些研究可以阐明 megalin 是否可以以一种或另一种方式作为治疗靶点来治疗肾脏疾病。