Altering expression of alpha 3 beta 1 integrin on podocytes of human and rats with diabetes

The adhesion molecule integrin alpha 3 beta 1 is the major receptor of podo cyte to the glomerular capillary basement membrane (GBM), Since progressive alteration of the glomerular extracellular matrix (ECM) compartment leadin g to GEM thickening is common in diabetic nephropathy, we investigated the cellular distribution of alpha 3 beta 1 integrin in podocytes of patients w ith diabetic nephropathy and streptozotocin-induced diabetic rats, and we e valuated the effects of high glucose on the cultured rat podocytes. Both hu man and rat kidneys were stained using the immunoelectron microscopy and im munoperoxidase technique with mouse monoclonal antibodies to human integrin alpha 3 subunit, The results showed that both the number of immunogold par ticles and the staining of integrin alpha 3 subunit on podocytes were weake r 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 stai ning 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 e xpression of integrin alpha 3 beta 1 on podocytes was suppressed in both hu man and rats with diabetes, possibly due to the effects of hyperglycemia, a nd the suppression became more severe with the duration of diabetes. (C) 20 00 Elsevier Science Inc. All rights reserved.