Altering expression of α3β1 integrin on podocytes of human and rats with diabetes

The adhesion molecule integrin alpha 3 beta 1 is the major receptor of podocyte to the glomerular capillary basement membrane (GBM), Since progressive alteration of the glomerular extracellular matrix (ECM) compartment leading to GEM thickening is common in diabetic nephropathy, we investigated the cellular distribution of alpha 3 beta 1 integrin in podocytes of patients with diabetic nephropathy and streptozotocin-induced diabetic rats, and we evaluated the effects of high glucose on the cultured rat podocytes. Both human and rat kidneys were stained using the immunoelectron microscopy and immunoperoxidase technique with mouse monoclonal antibodies to human integrin alpha 3 subunit, The results showed that both the number of immunogold particles and the staining of integrin alpha 3 subunit on podocytes were weaker in patients with diabetic nephropathy than those of control kidneys. The staining of alpha 3 on podocytes in the poorly-controlled diabetic rats was also weaker after one and three months of hyperglycemia, However, the staining was identical to controls in rats with only one week of hyperglycemia. High glucose (25 mM) but not streptozotocin in vitro suppressed the alpha 3 expression of cultured rat podocytes, Our results demonstrated that the expression of integrin alpha 3 beta 1 on podocytes was suppressed in both human and rats with diabetes, possibly due to the effects of hyperglycemia, and the suppression became more severe with the duration of diabetes. (C) 2000 Elsevier Science Inc. All rights reserved.