Expression of subunits of the metalloendopeptidase meprin in the
renal cortex in experimental hydronephrosis.
Ricardo, Sharon D., Judith S. Bond, Gary D. Johnson, John Kaspar, M.
D., Jonathan R. Diamond.
Departments of Medicine, Biochemistry and Molecular Biology,
Surgery, and Cellular and Molecular Physiology, Milton S. Hershey
Medical Center and the Pennsylvania State University College of
Medicine, P.O. Box 850, Hershey, PA 17033.
APStracts 2:0206F, 1995.
Meprin A is a metalloendopeptidase in proximal tubular epithelium of
rodents that is capable of hydrolyzing a great variety of peptides
and proteins. The aim of the present investigation was to investigate
effects of ureteral ligation on the expression of meprin subunits.
Ureteral ligation resulted in marked decreases in the expression of
both [alpha] and [beta] meprin subunits within 12 h of ureteral
obstruction. Even greater down-regulation of expression of meprin
[alpha] and [beta] mRNA was noted at 24, 48, and 96 h after ureteral
ligation. The greatest decrease in meprin mRNA expression in
obstructed kidneys over contralateral unobstructed control kidneys
(CUK) occurred at 24 h post-unilateral ureteral obstruction (UUO) for
the meprin [alpha] subunit (20-fold decrease compared with controls),
and at 48 h for the meprin [beta] subunit (90-fold decrease). On
immunolabeling, the intensity for the two meprin subunits at the
corticomedullary junction was dramatically decreased at 24 to 96 h
after ureteral ligation in contrast to the CUK specimens. Results of
in situ hybridization indicated that the CUK specimens expressed
meprin [beta] mRNA at the corticomedullary junction, while the
obstructed kidneys exhibited a decrease in mRNA signal for meprin
[beta]. There was a steady increase in the interstitial macrophage
number in UUO rat kidneys over the 96 h of evaluation post-UUO. ED-1
-positive macrophages were observed almost exclusively in the
peritubular cortical interstitial space in a ring-like pattern with a
preponderance of macrophage clusters around glomeruli. Unexpectedly,
after R-UUO, the interstitial macrophage number remained higher than
controls, despite the demonstrable decompression of the renal pelvis
and calicyeal system. In summary, this investigation demonstrates
down-regulation of meprin [alpha] and [beta] within hours of UUO and
indicates a novel tubular response to ureteral obstruction.
Received 18 July 1995; accepted in final form 27 November 1995.
APS Manuscript Number F236-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95