The distribution and regulation of integrin-linked kinase in normal and diabetic kidneys
The distribution and regulation of integrin-linked kinase in normal and diabetic kidneys
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DOI：
10.1016/s0002-9440(10)63020-9
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发表时间：
2001-11-01
影响因子：
6
通讯作者：
Wu, CY
中科院分区：
文献类型：
--
作者：
Guo, LD;Sanders, PW;Wu, CY
细胞粘附和细胞外基质沉积的改变是糖尿病肾小球硬化的标志。整合素连接激酶（integrin -linked kinase， ILK）是最近发现的一种整合素细胞质结合蛋白，参与细胞粘附和细胞外基质沉积的调节。为了开始研究ILK是否参与糖尿病肾小球硬化的发病机制，我们分析了ILK在正常肾脏、糖尿病肾脏以及离体肾小球系膜细胞中的分布和调控。我们发现ILK通常在内脏上皮细胞中高浓度表达。在糖尿病肾小球中，ILK在系膜中的表达。急剧增加。ILK水平的升高与弥漫性系膜扩张有关。在以晚期结节硬化和全局硬化为主的肾小球中，ILK水平降低，表明ILK表达的增加可能与相对早期的肾小球硬化有关。此外，我们发现系膜细胞暴露于高浓度葡萄糖显著增加ILK水平。最后，我们发现ILK定位于与系膜纤维连接蛋白基质密切接触的细胞膜区域。这些结果表明，ILK可能参与了糖尿病肾小球硬化发病过程中对高血糖反应的系膜基质扩张。
Alteration in cell adhesion and extracellular matrix deposition is a hallmark of diabetic glomerulosclerosis. Integrin-linked kinase (ILK) is a recently identified integrin cytoplasmic-binding protein that has been implicated in the regulation of cell adhesion and extracellular matrix deposition. To begin to investigate whether ILK is involved in the pathogenesis of diabetic glomerulosclerosis, we have analyzed the distribution and regulation of ILK in normal and diabetic kidneys as well as in isolated mesangial cells. We have found that ILK is normally expressed at high concentration in visceral epithelial cells. In diabetic glomeruli, ILK expression in the mesangium. is dramatically increased. The increase in ILK level is associated with diffuse mesangial expansion. In glomeruli where advanced nodular sclerosis and global sclerosis were dominant, ILK level was reduced, suggesting that the increase in ILK expression likely associates with relatively early glomerulosclerosis. Additionally, we have found that exposure of mesangial cells to high concentrations of glucose significantly increased the ILK level. Finally, we show that ILK localizes to regions of cell membranes that are in close contact with mesangial fibronectin matrix. These results suggest that ILK is likely involved in mesangial matrix expansion in response to hyperglycemia in the pathogenesis of diabetic glomerulosclerosis.