エンドサイトーシス受容体メガリン : 糖尿病性腎症・メタボリック症候群関連腎症および尿毒症病態における役割

概要

論文の詳細を見る
Megalin is a multiligand endocytotic receptor expressed in the proximal tubule cells and play a major role in the renal protein metabolism. It was found to interact with intracellular adaptor proteins for endocytotic signaling, and other membrane proteins such as cubilin and Na^+-H^+exchanger isoform 3 for cooperative functions. We found that megalin regulates the endocytosis of advanced glycation end products which are involved in the pathogenesis of diabetic nephropathy. We also found that it mediates the proximal tubular uptake of leptin, an adipocytokine, and liver-type fatty acid binding protein, which may play a role in the development of "metabolic syndrome-related nephropathy". Further studies on the molecular mechanisms of megalin-mediated renal protein metabolism are needed to develop novel therapeutic strategies for the diseases. Megalin also mediates the renal metabolism of uremic toxin proteins such as β_2-microglobulin that accumulates in dialysis patients and causes amyloidosis. Using subcutaneous implantation of megalin-expressing cells, we developed a cell therapy model to remove circulating β_2-microglobulin in the experimental renal failure. We are currently under study for the future clinical application.
新潟大学の論文
2005-01-10