OSTEOPONTIN EXPRESSION IN ANGIOTENSIN-II-INDUCED TUBULOINTERSTITIAL NEPHRITIS
OSTEOPONTIN EXPRESSION IN ANGIOTENSIN-II-INDUCED TUBULOINTERSTITIAL NEPHRITIS
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DOI：
10.1038/ki.1994.67
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发表时间：
1994-02-01
影响因子：
19.6
通讯作者：
JOHNSON, RJ
中科院分区：
文献类型：
--
作者：
GIACHELLI, CM;PICHLER, R;JOHNSON, RJ
骨桥蛋白是一种含有精氨酸-甘氨酸-天冬氨酸（RGD）的分泌性磷蛋白，最近显示当皮下注射小鼠时刺激局部巨噬细胞流入。我们通过原位杂交和免疫组化检测血管紧张素II输注对大鼠肾损伤和骨桥蛋白表达的影响。在肾小管和间质细胞的病理变化之前，主要在远端小管、集合管和Bowman囊的上皮细胞中观察到肾骨桥蛋白蛋白和mRNA水平的急剧增加。虽然皮质和髓质显示骨桥蛋白水平增加，但这种作用在肾皮质中最明显，肾皮质通常显示很少的组成性骨桥蛋白表达。有趣的是，表达高水平骨桥蛋白的肾脏区域与单核细胞/巨噬细胞积聚的部位相关。这些观察结果，再加上最近的发现，骨桥蛋白可能是一种促炎蛋白，表明骨桥蛋白的过度表达可能会促进单核细胞/巨噬细胞在肾小管间质损伤的网站的积累。
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.