Serial alterations of glomerular matrix-degrading metalloproteinase activity in anti-thymocyte-induced glomerulonephritis in rats.
In the present study, we investigated the serial changes of glomerular metalloproteinase (GMP) activity in antithymocyte-induced glomerulonephritis (Thy.1 GN) in rats. GMP activity was determined by the measurement of EDTA-inhibitable gelatinolytic activity toward tritiated gelatin as substrate. Thy.1 GN was made by injection of antithymocyte serum into female Wistar rats and glomeruli were separated by a graded sieving method. Glomeruli were homogenized with sonication, and then the supernatant was used for the assay of GMP activity and substrate study. GMP activity was reduced on day 1 and at week 2 compared with controls, and returned to the control level by week 9. On light-microscopic examination, diffuse and focal glomerular ECM expansion were observed at weeks 2 and 4, respectively. These changes disappeared by week 9. With the use of several substrates labeled with tritium, GMP was observed to degrade type IV collagen, fibronectin and casein as well as gelatin, but not type I collagen. In conclusion, attenuated GMP activity may be one of the causes of glomerular ECM expansion in Thy.1 GN, because GMP was capable of degrading the components of glomerular ECM.
Sato
Y
Y
First Department of Internal Medicine, Miyazaki Medical College, Kiyotake, Japan.
Fujimoto
S
S
Hamai
K
K
Eto
T
T
D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced / Q000201:enzymology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007668:Kidney / Q000166:cytology / Q000473:pathology; D007678:Kidney Glomerulus / Q000201:enzymology; D008666:Metalloendopeptidases / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012967:Sodium Dodecyl Sulfate; D013379:Substrate Specificity
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D012967:Sodium Dodecyl Sulfate; D008666:Metalloendopeptidases