Expression of alpha-actinin-4 in human diabetic nephropathy

Abstract

Background: Alpha-actinin-4 is an actin filament, crosslinking, protein that interacts with intercellular adhesion molecules. Recent animal studies, suggested that alpha-actinin-4 is an essential component of the glomerular filtration barrier. However, little is known about its expression in human diabetic nephropathy (DN). Methods: Renal biopsy tissues were obtained from 17 patients with DN. We determined the mRNA and protein expression levels of alpha-actinin-4 by in situ hybridization and inummohistochemistry. The histopathological severity of DN was classified into two groups: mild and moderate mesangial expansion groups. We also measured urinary protein excretion and creatinine clearance. Results: Podocytes were positively stained for alpha-actinin-4 mRNA and protein. In the glomeruli, the percentage of cells positive for alpha-actinin-4 mRNA was significantly lower in moderate mesangial expansion group than in mild mesangial expansion group and control. The percentage of immunohistochemically positive area for alpha-actinin-4 protein in moderate mesangial expansion group was significantly lower than in mild mesangial expansion group and control. The percentage of cells positive for alpha-actinin-4 mRNA and area positive for the protein correlated inversely with severity of proteinuria. Conclusion: Our results suggest that low expression levels of alpha-actinin-4 mRNA and protein are linked to the progression of glomerulopathy and proteinuria in human DN. © 2008 The Japanese Society of Internal Medicine.