| Research Abstract |
We have succeeded in cloning the rat homologue of nephrin which is a product of gene responsible for Finnish-type congenital nephrotic syndrome and concluded that proteinuria-inducing monoclonal anti-rat slit membrane antibody 5-1-6 recognizes the extracellular sites of rat nephrin. In 5-1-6 nephropathy, induced by a single injection of 5-1-6, and also in PAN nephrosis, representative rat model for nephrotic syndrome, the expression of nephrin was decreased already in early stage before start of proteinuria, which suggested that the decrease of nephrin expression is not the result but cause of proteinuria and nephrin abnormality is intimately related not only to congenital but also acquired renal lesions, especially the induction of proteinuria.
We have succeeded also in cloning the recently reported podocin, a product of gene responsible to familial FSGS. In 5-1-6 nephropathy as well as in PAN nephrosis immunofluorescent positive staining pattern was changed from pseudo-linear to granular just as in the case of nephrin. In 5-1-6 nephropathy podocin was co-localized with nephrin, but not in PAN nephropathy. The decrease in the expression of podocin at the mRNA level was recognized in 5-1-6 nephropathy.
In conclusion, podocin has been demonstrated to play an important role to keep the normal glomerular permoselectivity and to be a therapeutical target molecule to be examined.
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