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From the Dipartimento di Medicina Interna,*
Università di Torino, Torino, Italy; the Dipartimento di Medicina
Interna,
Cattedra di Nefrologia,
Università di Genova, Genova, Italy; the Dipartimento di Scienze
Cliniche e Biologiche,
Università
dell’Insubria, Varese, Italy; the Department of
Biochemistry,
University of Oulu, Oulu,
Finland; and the Department of Medical Biochemistry and
Biophysics,¶
Karolinska Institute,
Stockholm, Sweden
We investigated the distribution of nephrin by immunofluorescence
microscopy in renal biopsies of patients with nephrotic syndrome: 13
with membranous glomerulonephritis (GN), 10 with minimal change
GN, and seven with focal segmental glomerulosclerosis. As
control, six patients with IgA GN without nephrotic syndrome
and 10 normal controls were studied. We found an extensive loss of
staining for nephrin and a shift from a podocyte-staining pattern to a
granular pattern in patients with nephrotic syndrome,
irrespective of the primary disease. In membranous GN, nephrin
was co-localized with IgG immune deposits. In the attempt to explain
these results, we investigated in vitro whether
stimuli acting on the cell cytoskeleton, known to be involved
in the pathogenesis of GN, may induce redistribution of nephrin
on the surface of human cultured podocytes. Aggregated but not
disaggregated human IgG4, plasmalemmal insertion of
membrane attack complex of complement, tumor necrosis
factor-
, and puromycin, induced the shedding of
nephrin with a loss of surface expression. This phenomenon was
abrogated by cytochalasin and sodium azide. These results suggest that
the activation of cell cytoskeleton may modify surface expression of
nephrin allowing a dislocation from plasma membrane to an extracellular
site.
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W. Huh, D. J. Kim, M.-K. Kim, Y. G. Kim, H.-Y. Oh, V. Ruotsalainen, and K. Tryggvason Expression of nephrin in acquired human glomerular disease Nephrol. Dial. Transplant., March 1, 2002; 17(3): 478 - 484. [Abstract] [Full Text] [PDF]
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H. Yuan, E. Takeuchi, and D. J. Salant Podocyte slit-diaphragm protein nephrin is linked to the actin cytoskeleton Am J Physiol Renal Physiol, April 1, 2002; 282(4): F585 - F591. [Abstract] [Full Text] [PDF]
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