Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes
Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes
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DOI：
10.2337/diabetes.52.10.2586
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发表时间：
2003-10-01
期刊：
影响因子：
7.7
通讯作者：
Makino, H
中科院分区：
文献类型：
--
作者：
Okada, S;Shikata, K;Makino, H
糖尿病肾病是导致终末期肾衰竭的主要原因。几种机制，包括蛋白激酶C激活、晚期糖基化终产物和过表达。转化生长因子（TGF）-β的表达与糖尿病肾病的发病机制有关。然而，炎症过程在糖尿病微血管并发症发病机制中的意义知之甚少。巨噬细胞的积聚和白细胞粘附分子和趋化因子的过度表达在糖尿病人肾组织中是突出的。我们以前证明，细胞间粘附分子（ICAM）-1介导的巨噬细胞浸润到糖尿病肾脏。在本研究中，为了研究ICAM-1在糖尿病肾病中的作用，我们用链脲佐菌素诱导ICAM-1缺陷（ICAM-1（-/-））小鼠和ICAM-1（+/+）小鼠糖尿病，并在6个月内检查肾脏病理学。糖尿病ICAM-1（-/-）小鼠巨噬细胞浸润明显低于ICAM-1（+/+）小鼠。糖尿病ICAM-1（-/-）小鼠的尿白蛋白排泄、肾小球肥大和系膜基质扩张显著低于糖尿病ICAM-1（+/+）小鼠。此外，TGF-β和IV型胶原在糖尿病ICAM-1（-/-）小鼠肾小球中的表达也受到抑制。提示ICAM-1在糖尿病肾病的发病中起重要作用。
Diabetic nephropathy is a leading cause of end-stage renal failure. Several mechanisms, including activation of protein kinase C, advanced glycation end products, and overexpression. of transforming growth factor (TGF)-beta, are believed to be involved in the pathogenesis of diabetic nephropathy. However, the significance of inflammatory processes in the pathogenesis of diabetic microvascular complications is poorly understood. Accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines are prominent in diabetic human kidney tissues. We previously demonstrated that intercellular adhesion molecule (ICAM)-1 mediates macrophage infiltration into the diabetic kidney. In the present study, to investigate the role of ICAM-1 in diabetic nephropathy, we induced diabetes in ICAM-1-deficient (ICAM-1(-/-)) mice and ICAM-1(+/+) mice with streptozotocin and examined the renal pathology over a period of 6 months. The infiltration of macrophages was markedly suppressed in diabetic ICAM-1(-/-) mice compared with that of ICAM-1(+/+) mice. Urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion were significantly lower in diabetic ICAM-1(-/-) mice than in diabetic ICAM-1(+/+) mice. Moreover, expressions of TGF-beta and type IV collagen in glomeruli were also suppressed in diabetic ICAM-1(-/-) mice. These results suggest that ICAM-1 is critically involved in the pathogenesis of diabetic nephropathy.