PODOCYTE PHENOTYPES AS DEFINED BY EXPRESSION AND DISTRIBUTION OF GLEPP1 IN THE DEVELOPING GLOMERULUS AND IN NEPHROTIC GLOMERULI FROM MCD, CNF, AND FSGS - A DEDIFFERENTIATION HYPOTHESIS FOR THE NEPHROTIC SYNDROME

Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membra ne protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell (VGEC) foot processes. Double lab el immunofluorescence, immunoelectron microscopy, and peroxidase immun ohistochemistry were used to map the GLEPP1 distribution in the develo ping glomerulus and in minimal-change nephropathy (MCN), congenital ne phrotic syndrome of the Finnish type, and focal-segmental glomeruloscl erosis (FSGS). In MCN GLEPP1 was shifted away from the glomerular base ment membrane on the apical cell membrane of effaced foot processes. T hese data are compatible with the previously suggested concept that MC N can be considered a form of dedifferentiation of the podocyte phenot ype. Similarly, changes seen in congenital nephrotic syndrome of the F innish type can be considered a consequence of failure to complete nor mal podocyte development. In FSGS glomeruli GLEPP1 was frequently abse nt from VGECs, even when no sclerosis was detectable in that glomerulu s. Therefore, in FSGS, VGECs may lose GLEPP1, and this loss appears to occur in the absence of scarring and may, therefore, precede the scar ring process. We speculate that a changed VGEC phenotype that does not express GLEPP1 might have properties similar to the early undifferent iated VGEC developmental phenotype. GLEPP1 distribution pattern and ab sence from glomeruli of individuals with nephrotic syndrome may, there fore, represent a useful phenotypic marker.