DISTRIBUTION OF INTEGRIN SUBUNITS IN HUMAN DIABETIC KIDNEYS

Integrins are cell-surface protein receptors that participate in cell adhesion to multiple extracellular matrix ligands, and consist of alph a and beta chain heterodimers. This study examined altered integrin di stribution in diabetic nephropathy by investigating 12 human diabetic kidney biopsies, which were compared with normal human kidney. Diabeti c nephropathy is characterized by mesangial expansion and progressive thickening of the glomerular basement membrane. Based on morphometric studies of mesangial expansion, diabetic nephropathy was determined to be moderate or severe. Three different patterns (P) of altered intens ity of integrin staining were observed. In the mesangial integrin P, t he intensity of integrin subunit staining of mesangial cells (alpha 1, alpha 2, alpha 3, beta 1, alpha v, alpha v beta 5) was increased in m oderate diabetic nephropathy and further increased in severe diabetic nephropathy. In the epithelial integrin P, integrin subunits localized to epithelial cells (alpha v, beta 3, alpha v beta 3, alpha v beta 5) were increased to the same extent in moderate and severe diabetic nep hropathy. In the endothelial integrin P, integrin subunits localized t o endothelial cells (alpha 3, alpha 5, alpha 6, beta 1) were increased in moderate diabetic nephropathy but returned to normal kidney staini ng intensity in severe diabetic nephropathy. From these observations, it was concluded that there is significant alteration in the expressio n of integrin subunits in diabetic nephropathy that is related to the severity of diabetic mesangial expansion, Additionally, the spectrum o f integrin subunit alteration appears to be unique to individual glome rular cell types. Given the role of integrins in cell-surface interact ions with extracellular matrix components, abnormalities in the expres sion of these molecules may be important in the pathogenesis of diabet ic nephropathy.