Monocyte chemoattractant protein-1 and macrophage infiltration in hypertensive kidney injury
Monocyte chemoattractant protein-1 and macrophage infiltration in hypertensive kidney injury
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DOI：
10.1046/j.1523-1755.2000.00424.x
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发表时间：
2000-12-01
影响因子：
19.6
通讯作者：
Mann, JFE
中科院分区：
文献类型：
--
作者：
Hilgers, KF;Hartner, A;Mann, JFE
背景我们研究了单核细胞趋化蛋白-1（MCP-1）是否在高血压肾硬化中表达，并检测了血管紧张素II 1型受体阻断剂对MCP-1表达和巨噬细胞（M Phi）浸润的影响。研究了两肾一夹（2K 1C）高血压大鼠，使用和不使用血管紧张素II 1型受体拮抗剂缬沙坦（3 mg/kg/天）治疗。在这些动物以及自发性高血压大鼠（SHR）、易卒中SHR（SHR-SP）、高血压mRen-2转基因大鼠（TGR）和各自的对照品系中，通过北方和西方印迹以及通过免疫组织化学研究肾脏中的MCP-1表达。计算肾小球和间质M Phis。在2K 1C大鼠的非夹肾，MCP-1的表达升高，在14和28天时，存在显着的M φ浸润。MCP-1定位于肾小球内皮细胞和上皮细胞、间质细胞和肾小管细胞、M Phis和血管平滑肌细胞。TGR肾组织中MCP-1的表达模式相似，而SHR和SHR-SP肾组织中MCP-1的表达并没有增加。缬沙坦降低了2K 1C肾组织中MCP-1的表达，但没有使其正常化，阻断了MCP-1蛋白的诱导，并显著减少了间质M Phi的浸润。MCP-1的表达增加血管紧张素II依赖性模型的高血压肾硬化症，是时间和空间相关的M φ浸润。血管紧张素II 1型受体介导MCP-1的诱导。
Background. We investigated whether monocyte chemoattractant protein-1 (MCP-1) is expressed in hypertensive nephrosclerosis, and tested the effect of angiotensin II type 1 receptor blockade on MCP-1 expression and macrophage (M Phi) infiltration.Methods. Rats with two-kidney, one-clip (2K1C) hypertension with and without treatment with the angiotensin II type 1 receptor antagonist valsartan (3 mg/kg/day) were studied. In these animals as well as in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP), hypertensive mRen-2 transgenic rats (TGR), and respective control strains, MCP-1 expression in the kidney was investigated by Northern and Western blots and by immunohistochemistry. Glomerular and interstitial M Phis were counted.Results. In the nonclipped kidney of 2K1C rats, MCP-1 expression was elevated at 14 and 28 days when significant M Phi infiltration was present. MCP-1 was localized to glomerular endothelial and epithelial cells, interstitial and tubular cells, M Phis, and vascular smooth muscle cells. A similar pattern of MCP-1 staining was present in TGR kidneys, whereas MCP-1 expression was not increased in SHR and SHR-SP. Valsartan reduced but did not normalize brood pressure, blocked the induction of MCP-1 protein in 2K1C kidneys, and decreased interstitial M Phi infiltration significantly.Conclusion. MCP-1 expression is increased in angiotensin II-dependent models of hypertensive nephrosclerosis and is temporally and spatially related to M Phi infiltration. The angiotensin II type 1 receptor mediates the induction of MCP-1.