| Nephrotic syndrome is a clinical presentation encountered in a wide range of renal disorders (idiopathic nephrotic syndrome, diabetic nephropathy, systemic lupus erythematosis, focal segmental glomerlosclerosis) having glomerular dysfunction as their common denominator. While the nephrotic syndrome may be associated with a variety of initiating mechanisms, it represents a final common pathway subsequent to morphologic alterations in cellular architecture of the glomerular filtration barrier. Specifically, when glomerular epithelial cells (podocytes) become challenged, extended podocyte pedicels undergo a stereotypic, morphological change involving contracted flattening. This retracting response pattern results in drastic changes in filtration slit width that effects the filtration sieving coefficient. Changes in the sieving coefficient result in alterations of solute (serum protein) flux across the filtration barrier.; Over the last several decades, comparisons between the histologic, ultrastructural and molecular findings in natural occurring human glomerular disorders and defined animal models have yielded valuable information into glomerular pathophysiology. However, while a fairly detailed picture of the phenotypic changes leading to proteinuria has emerged, the underlying molecular events and responses that occur during podocyte injury and repair have yet to be established. Unraveling these molecular mechanisms has proved most difficult, mainly due to an elemental inability to generate pure podocyte cell culture systems retaining both the highly specialized architectural features, as well as a full expression of domain-restricted proteins and glycolipids. A major shortcoming, failure to generate a versatile and representative cell line has necessitated the further development of defined animal models.; In this study, adaptation of a previously described in vivo model of neuraminidase-induced glomerular injury is described in the rat. Information derived from the initial pilot studies has been used to formulate the hypothesis that loss of glomerular sialic acid, concomitant with functional glomerular damage, results in a re-sialylation event associated with sequentially increased levels of glomerular linkage-specific sialyltransferase transcript levels and activity. The results of these experiments provide insight into specific molecular responses of podocytes to injury, in addition to demonstrating the versatility of this animal model for descriptive and mechanistic studies regarding podocyte sialobiology. |
