Kulkarni Kalyani, Hussain Tahir
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas.
J Am Soc Nephrol. 2025 Feb 1;36(2):293-300. doi: 10.1681/ASN.0000000572. Epub 2024 Nov 15.
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.
巨蛋白是近端小管中的一种内吞受体，可重吸收肾脏中滤过的蛋白质。内吞作用后巨蛋白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。在生理和病理生理条件下，肾脏中巨蛋白的表达会发生动态变化。受体和各种效应器信号成分调节巨蛋白的表达，并可能影响其功能。对巨蛋白的基因操作和罕见突变表明，巨蛋白表达/功能的缺乏或缺陷会导致肾小管蛋白尿和白蛋白尿。然而，巨蛋白在与肥胖、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。为了解决这些问题，动物和人体研究表明巨蛋白是肾病的一种保护性、损伤性和潜在的尿液标志物。本文综述了有关巨蛋白表达调控以及在实验和临床条件下巨蛋白在肾脏病理生理学中作用的文献。此外，本综述明确指出需要开展研究，以阐明巨蛋白是否能以某种方式作为治疗靶点来治疗肾脏疾病。
