Decreased matrix metalloproteinase activity in the kidneys of hereditary nephrotic mice (ICGN strain).
Abnormalities of extracellular matrix (ECM) metabolism, i.e., overproduction and/or inhibition of ECM breakdown, may contribute to progression of fibrotic degeneration in the kidney. Earlier studies revealed that major ECM components, type I, III, and IV collagens, etc., were accumulated in glomeruli and tubulointerstitium in kidneys of Institute of Cancer Research (ICR) derived glomerulonephritis (ICGN) mice which are a novel inbred strain of mice with a hereditary nephrotic syndrome of unknown etiology and are considered to be a good model of human idiopathic nephrotic syndrome. In the present study, we compared the activities of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components, in the kidneys of aged ICGN mice and age-matched ICR mice as normal controls. We biochemically measured interstitial collagenase (MMP-1), gelatinase (MMP-2 and MMP-9), and stromelysin (MMP-3) activities in the kidney tissues. Lower activities of MMP-1 and MMP-2 and MMP-9 were demonstrated in the kidneys of ICGN mice as compared with those of ICR mice, but there were no significant differences in the MMP-3 activities between these strains. These results show that decreased MMP activities cause abnormal accumulation of ECM in ICGN mouse kidneys.
Uchio
K
K
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University, Kyoto, Japan.
Manabe
N
N
Tamura
K
K
Miyamoto
M
M
Yamaguchi
M
M
Ogura
A
A
Yamamoto
Y
Y
Miyamoto
H
H
D000375:Aging; D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005921:Glomerulonephritis / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000201:enzymology* / Q000254:growth & development / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains
D016326:Extracellular Matrix Proteins; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1