Role of proteinases in renal hypertrophy and matrix accumulation.
Graded compensatory renal growth was induced either by unilateral (UNX) or 5/6 nephrectomy (5/6-NX). Over the experimental period of 16 weeks, kidney weight increased by 59% in SHAM animals, while the remaining kidney in UNX rats more than doubled its initial weight. The hypertrophic response was most pronounced in the remnant kidney after 5/6-NX with a four fold increment in kidney weight. Morphologically glomerular volume increased moderately after UNX (+27%), while 5/6-NX was associated with marked glomerular hypertrophy (+87%). Significant focal sclerosis was found in 11% of glomeruli in the remaining kidney after UNX. By contrast 83% of glomeruli wre sclerosed in the remnant kidney after 5/6-NX. In parallel, there was a significant increase in the glomerular protein/DNA ratio (+23%) in 5/6-NX but not in UNX animals. These glomerular alterations were associated with lower glomerular cysteine and metalloproteinase activities (collagenase, -57%; gelatinase, -49%) in 5/6-NX rats, while UNX rats had normal glomerular proteinase activities. In terms of tubular proteinases, cathepsin activities were significantly lower in UNX rats (cath. L+B, -38%; cath. B, -37%; cath. H, -27%) and more so after 5/6-nephrectomy (cath. L+B, -72%; cath. B, -73%; cath. H, -73%), while metalloproteinase activities were only reduced in 5/6-NX rats (collagenase, -35%; gelatinase, -58%). These findings demonstrate that kidney hypertrophy is associated with reduction in renal proteinase activities.(ABSTRACT TRUNCATED AT 250 WORDS)
Schafer
L
L
Department of Internal Medicine, University of Münster, Germany.
Lorenz
T
T
Daemmrich
J
J
Heidland
A
A
Schaefer
R M
RM
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D004247:DNA / Q000032:analysis; D010450:Endopeptidases / Q000378:metabolism*; D005109:Extracellular Matrix / Q000201:enzymology* / Q000473:pathology; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009929:Organ Size; D011506:Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D011506:Proteins; D004247:DNA; D000135:Acid Phosphatase; D010450:Endopeptidases