Human and rat mesangial cell receptors for glucose-modified proteins: potential role in kidney tissue remodelling and diabetic nephropathy.
Human and rat mesangial cell receptors for glucose-modified proteins: potential role in kidney tissue remodelling and diabetic nephropathy.
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DOI：
10.1084/jem.174.4.931
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发表时间：
1991-10-01
期刊：
影响因子：
--
通讯作者：
Vlassara H
中科院分区：
文献类型：
--
作者：
Skolnik EY;Yang Z;Makita Z;Radoff S;Kirstein M;Vlassara H
晚期糖基化终产物（AGEs）来源于葡萄糖对蛋白质的非酶作用。已经发现AGEs在糖尿病患者的组织蛋白上积累，并且它们的积累被认为在糖尿病并发症的发展中起作用。巨噬细胞和内皮细胞含有age特异性受体的发现使我们研究系膜细胞（MCs）是否也具有识别和加工age的机制。从大鼠和人MCs中分离的膜提取物被发现以饱和方式结合age -牛血清白蛋白（BSA），结合亲和力为2.0 +/- 0.4 x 10(6) M-1 （500 nM）。这种结合对AGE加合物是特异性的，因为AGE修饰的I型胶原和核糖核酸酶都竞争性地抑制了125I-AGE-BSA与MC膜的结合，而未修饰的蛋白则没有竞争。AGE蛋白结合之后是配体的缓慢内化和降解。MC膜提取物的配体印迹显示了三种不同的年龄结合膜蛋白，分别为50、40和30 kD。MCs在各种age修饰的基质蛋白上的生长导致MCs功能的改变，如纤维连接蛋白的增加和增殖的减少所证明的那样。这些结果表明，age修饰蛋白与MCs的相互作用可能在体内促进糖尿病肾病中发挥潜在作用。
Advanced glycosylation endproducts (AGEs) are derived from the nonenzymatic addition of glucose to proteins. AGEs have been found to accumulate on tissue proteins in patients with diabetes, and their accumulation is thought to play a role in the development of diabetic complications. The finding that macrophages and endothelial cells contain AGE-specific receptors led us to examine whether mesangial cells (MCs) also possess a mechanism for recognizing and processing AGEs. Membrane extracts isolated from rat and human MCs were found to bind AGE-bovine serum albumin (BSA) in a saturable fashion, with a binding affinity of 2.0 +/- 0.4 x 10(6) M-1 (500 nM). The binding was specific for the AGE adduct, since AGE-modified collagen I and ribonuclease both competitively inhibited 125I-AGE-BSA binding to MC membranes, while the unmodified proteins did not compete. Binding of AGE proteins was followed by slow internalization and degradation of the ligand. Ligand blotting of MC membrane extracts demonstrated three distinct AGE-binding membrane proteins of 50, 40, and 30 kD. Growth of MCs on various AGE-modified matrix proteins resulted in alterations in MC function, as demonstrated by enhanced production of fibronectin and decreased proliferation. These results point to the potential role that the interaction of AGE-modified proteins with MCs may play in vivo in promoting diabetic kidney disease.