Giachelli C M, Pichler R, Lombardi D, Denhardt D T, Alpers C E, Schwartz S M, Johnson R J
Pathology Department, University of Washington, Seattle.
Kidney Int. 1994 Feb;45(2):515-24. doi: 10.1038/ki.1994.67.
Osteopontin is an arginine-glycine-aspartate (RGD) containing secreted phosphoprotein recently shown to stimulate a local macrophage influx when injected subcutaneously in mice. We examined the effect of angiotensin II infusion on renal injury and osteopontin expression in the rat kidney by in situ hybridization and immunohistochemistry. Preceding pathologic changes in tubular and interstitial cells, a dramatic increase in renal osteopontin protein and mRNA levels was observed primarily in epithelial cells of the distal tubules, collecting ducts and Bowman's capsule. Although both cortex and medulla showed increased osteopontin levels, the effect was most pronounced in the renal cortex which normally showed very little constitutive osteopontin expression. Interestingly, regions of the kidney expressing high osteopontin levels correlated with sites of monocyte/macrophage accumulation. These observations, coupled with recent findings that osteopontin may be a pro-inflammatory protein, suggests that osteopontin over-expression may facilitate monocyte/macrophage accumulation at the sites of renal tubulointerstitial injury.
骨桥蛋白是一种含精氨酸-甘氨酸-天冬氨酸（RGD）的分泌性磷蛋白，最近研究表明，将其皮下注射到小鼠体内时可刺激局部巨噬细胞流入。我们通过原位杂交和免疫组织化学方法，研究了输注血管紧张素II对大鼠肾脏损伤及骨桥蛋白表达的影响。在肾小管和间质细胞出现病理变化之前，主要在远端小管、集合管和鲍曼囊的上皮细胞中观察到肾骨桥蛋白蛋白和mRNA水平显著增加。虽然皮质和髓质的骨桥蛋白水平均升高，但在通常骨桥蛋白组成性表达很少的肾皮质中，这种效应最为明显。有趣的是，肾脏中骨桥蛋白水平高的区域与单核细胞/巨噬细胞聚集部位相关。这些观察结果，再加上最近发现骨桥蛋白可能是一种促炎蛋白，提示骨桥蛋白过度表达可能促进单核细胞/巨噬细胞在肾小管间质损伤部位的聚集。
