Nephrol Dial Transplant (2004) 19: 844-851
Nephrol Dial Transplant Vol. 19 No. 4 © ERA-EDTA 2004; all rights reserved
Original Article
Expression of 
-actinin-4 in acquired human nephrotic syndrome: a quantitative immunoelectron microscopy study
1Renal Research Unit, 2Department of Histopathology and 3Department of Renal Medicine, St James's University Hospital, The Leeds Teaching Hospitals NHS Trust, Leeds, UK
Correspondence and offprint requests to: Dr N. P. Goode, Renal Research Unit, Clinical Sciences Building, St James's University Hospital, Leeds LS9 7TF, UK. Email: n.p.goode{at}leeds.ac.uk
Background. The molecular basis for the alteration of glomerular podocyte phenotype in nephrotic syndrome probably involves adaptive changes of the actin cytoskeleton. 
-Actinin-4 is an actin cross-linking protein that also interacts with intra- and intercellular adhesion molecules and elements of the transmembrane signal transduction pathway and is implicated in nephrotic syndrome by animal models and human genetic studies.
Methods. We have performed the first quantitative immunoelectron microscopy study of -actinin-4 expression in humans, analysing 12 cases of minimal change nephrosis (MCNS) and 16 cases of idiopathic membranous nephropathy (MGN), and comparing this with expression in normal tissue from seven nephrectomies (Nx). -Actinin-4 was visualized by immunogold labelling of plastic-embedded whole glomerular cross-sections, and analysed using LUCIA software.
Results. Despite podocyte effacement, -actinin-4 expression (group mean±1 SD) in MCNS was similar to that seen in normal Nx podocytes. In contrast, -actinin-4 expression in MGN was significantly higher than in MCNS or Nx (P<0.001). Furthermore, in MGN cases showing a segmental deposition, expression of -actinin-4 was significantly higher only in those capillary loop segments containing deposits, whereas in those segments without deposits expression was unchanged compared with that seen in Nx (P<0.001). -Actinin-4 expression was higher in MGN cases where subepithelial deposits abutted podocyte cytoplasm, and lower in disease stages where deposits were contained within the glomerular basement membrane or were being reabsorbed.
Conclusions. Elevated -actinin-4 expression is observed only in MGN, and only in areas of subepithelial deposits. Further investigation into the cause of this may reveal insights into the pathogenesis of acquired nephrosis.
Keywords: -actinin-4; membranous nephropathy; minimal change nephrosis; nephrotic syndrome; podocyte
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