Abstract
Podocytes serve as the final barrier to urinary protein loss through a highly specialized structure called a slit membrane and maintain foot process and glomerular basement membranes. Podocyte injury results in progressive glomerular damage and accelerates sclerotic changes, although the exact mechanism of podocyte injury is still obscure. We focus on the staining gap (podocin gap) defined as the staining difference between podocin and synaptopodin, which are normally located in the foot process. In puromycin aminonucleoside nephrosis rats, the podocin gap is significantly increased (p < 0.05) and podocin is translocated to the cytoplasm on days 7 and 14 but not on day 28. Surprisingly, the gap is also significantly increased (p < 0.05) in human kidney biopsy specimens of poor-prognosis IgA nephropathy patients. This suggests that the podocin gap could be a useful marker for classifying the prognosis of IgA nephropathy and indicating the translocation of podocin to the cytoplasm. Next, we find more evidence of podocin trafficking in podocytes where podocin merges with Rab5 in puromycin aminonucleoside nephrosis rats at day 14. In immunoelectron microscopy, the podocin positive area was significantly translocated from the foot process areas to the cytoplasm (p< 0.05) on days 7 and 14 in puromycin aminonucleoside nephrosis rats. Interestingly, podocin is also translocated to the cytoplasm in poor-prognosis human IgA nephropathy. In this paper, we demonstrate that the translocation of podocin by endocytosis could be a key traffic event of critical podocyte injury and that the podocin gap could indicate the prognosis of IgA nephropathy.
Highlights
Podocytes are specialized epithelial cells constituting an essential part of the glomerular filtration barrier
We demonstrate that the translocation of podocin by endocytosis could be a key traffic event of critical podocyte injury and that the podocin gap could indicate the prognosis of IgA nephropathy
We demonstrated that podocin was translocated from the slit diaphragm (SD) area to the cytoplasm area by the endocytosis pathway in PAN rats and in the immunoglobulin A nephropathy (IgAN)-poor prognosis group
Summary
Podocytes are specialized epithelial cells constituting an essential part of the glomerular filtration barrier. Their interdigitated foot processes, connected by a slit diaphragm (SD), together with fenestrated endothelial cells and an intervening basement membrane, form the filtration barrier. The importance of podocyte integrity in the pathogenesis of nephrotic syndrome is best illustrated by the identification of human diseases causing mutations in genes encoding nephrin, podocin and CD2AP that span and stitch together foot processes of neighboring podocytes (Kestila et al 1998; Ruotsalainen et al 1999; Boute et al 2000). NPHS2 mutations cause several diseases with an interference of podocin intercellular trafficking (Roselli et al 2004)
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