Dh. Yang et al., GLOMERULAR EPITHELIAL PROTEIN-1 AND PODOCALYXIN-LIKE PROTEIN-1 IN INFLAMMATORY GLOMERULAR-DISEASE (CRESCENTIC NEPHRITIS) IN RABBIT AND MAN, Laboratory investigation, 74(3), 1996, pp. 571-584
The podocyte is the cell responsible in large part for maintaining the
glomerular filtration barrier. Glomerular epithelial protein 1 (GLEPP
1) is a novel receptor-like transmembrane protein tyrosine phosphatase
present on the apical surface of podocyte foot processes. Podocalyxin
-like protein 1 (PCLP1) is a transmembrane sialoglycoprotein which is
also present on the foot process apical surface as well as on the surf
ace of endothelial cells. GLEPP1 and PCLP1 are thought to play a role
in regulating the structure and function of podocyte foot processes. G
lomerular injury affecting the podocyte is likely to be reflected by c
hanges in these proteins. GLEPP1 distribution in human renal biopsy wi
th inflammatory glomerular disease and crescent formation was examined
by immunocytochemistry. A model of inflammatory glomerular injury ind
uced by guinea pig anti-rabbit basement membrane (anti-GEM) antibody w
as used to examine the distribution and amount of GLEPP1 and PCLP1 mRN
A and protein. A biopsy study was done to determine whether the extent
of GLEPP1 depletion from glomeruli at early time points (Day 7) would
predict the severity of crescent formation at Day 30. Glomeruli from
human renal biopsies with crescentic nephritis showed focal to diffuse
disappearance of GLEPP1 protein. No GLEPP1 was present within the cel
lular crescent. By Day 4 of the rabbit anti-GBM model, before cellular
crescents had formed, GLEPP1 protein was reduced from 127 +/- 28 x 10
(7) to 30 +/- 5 x 10(7) molecules per glomerulus (p < 0.001), and GLEP
P1 mRNA was reduced by 62% (p < 0.05). In contrast, at this time there
was no significant reduction of PCLP1 protein from the normal number
of 309 x 10(9) molecules per glomerulus and the PCLP1 mRNA level had n
ot decreased. At Day 4, podocyte foot processes were effaced and prote
inuria was present. Glomerular culture supernatants from Day 4 rabbits
caused a reduction in GLEPP1 but not PCLP1 protein expression by cult
ured normal glomeruli, showing that a soluble factor was produced at D
ay 4 which reduced the number of GLEPP1 molecules in glomeruli. There
was no detectable proteolysis of GLEPP1 or PCLP1 in glomeruli and no i
ncrease in GLEPP1 or PCLP1 excretion in urine. Therefore, the reductio
n in glomerular GLEPP1 was associated with reduced synthetic capacity.
The proportion of glomeruli with reduced GLEPP1 at Day 7 of the model
was significantly associated with the percent of glomeruli which had
formed crescents at Day 30 (r = 0.86, p < 0.0001). GLEPP1 appears to b
e a sensitive indicator of glomerular injury during inflammation in ma
n and in the rabbit model. A reduction in amount of GLEPP1 is associat
ed with worse outcome for the glomerulus.