Kaneto H, Morrissey J, McCracken R, Reyes A, Klahr S
Department of Medicine, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
Miner Electrolyte Metab. 1998;24(4):227-37. doi: 10.1159/000057375.
Osteopontin is a bone protein also expressed in other tissues. Increased osteopontin is thought to be associated with tissue inflammation. We used immunocytochemical analyses and polymerase chain reaction amplification of mRNA to examine osteopontin expression and regulation in unilateral ureteral obstruction (UUO) in rats, a model of inflammatory kidney disease. In the obstructed kidney, osteopontin mRNA and protein were significantly increased. The increase reached 4-fold after 1 day of UUO and persisted at this level for the 5-day duration of UUO. Immunocytochemical analyses showed increased osteopontin protein in tubular cells of the obstructed kidney cortex from days 1 through 5 of UUO. No such significant increase was apparent in the glomerulus or interstitium. Increased osteopontin mRNA and protein likewise occurred in the tubular cells of the obstructed kidney of rats that had undergone whole-body irradiation to eliminate macrophage infiltration into the experimental kidney. Purified osteopontin was found to be a chemoattractant for macrophages isolated from the rat peritoneum. Enalapril treatment, which decreases macrophage infiltration of the obstructed kidney, had no effect on the increase in osteopontin mRNA but significantly attenuated the increase in protein in tubular cells. Western blot analysis of whole cortical homogenates revealed that the osteopontin antibody recognized one protein of 67 kD. The amount of this protein was substantially decreased in kidney homogenates obtained from enalapril-treated compared to untreated animals. Increased osteopontin synthesis may, therefore, contribute in part to the inflammatory response that characterizes obstructive nephropathy.
骨桥蛋白是一种在骨骼中表达的蛋白质，也在其他组织中表达。骨桥蛋白水平升高被认为与组织炎症有关。我们使用免疫细胞化学分析和mRNA的聚合酶链反应扩增来检测大鼠单侧输尿管梗阻（UUO）（一种炎症性肾病模型）中骨桥蛋白的表达和调节。在梗阻的肾脏中，骨桥蛋白mRNA和蛋白质显著增加。UUO 1天后增加达到4倍，并在UUO持续的5天内维持在该水平。免疫细胞化学分析显示，在UUO的第1天至第5天，梗阻肾皮质的肾小管细胞中骨桥蛋白增加。在肾小球或间质中未观察到如此显著的增加。在接受全身照射以消除巨噬细胞浸润到实验肾脏的大鼠梗阻肾的肾小管细胞中，骨桥蛋白mRNA和蛋白质同样增加。发现纯化的骨桥蛋白是从大鼠腹膜分离的巨噬细胞的趋化剂。依那普利治疗可减少巨噬细胞浸润到梗阻的肾脏中，对骨桥蛋白mRNA的增加没有影响，但显著减弱了肾小管细胞中蛋白质的增加。对整个皮质匀浆的蛋白质免疫印迹分析显示，骨桥蛋白抗体识别一种67 kD的蛋白质。与未治疗的动物相比，从依那普利治疗的动物获得的肾脏匀浆中这种蛋白质的量显著减少。因此，骨桥蛋白合成增加可能部分导致了梗阻性肾病的炎症反应。
