The distribution and regulation of integrin-linked kinase in normal and diabetic kidneys

Alteration in cell adhesion and extracellular matrix deposition is a hallma rk of diabetic glomerulosclerosis. Integrin-linked kinase (ILK) is a recent ly 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 diabet ic 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 visce ral epithelial cells. In diabetic glomeruli, ILK expression in the mesangiu m. 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 glom erulosclerosis. Additionally, we have found that exposure of mesangial cell s to high concentrations of glucose significantly increased the ILK level. Finally, we show that ILK localizes to regions of cell membranes that are i n close contact with mesangial fibronectin matrix. These results suggest th at ILK is likely involved in mesangial matrix expansion in response to hype rglycemia in the pathogenesis of diabetic glomerulosclerosis.