Increased activity and expression of matrix metalloproteinase-9 in a rat model of distal colitis.
Matrix metalloproteinases may play a role in tissue remodelling and destruction associated with inflammation. We investigated activity and expression of matrix metalloproteinases in a rat model of colitis and tested the therapeutic potential of a synthetic inhibitor (CGS-27023-A). Colitis was induced by dextran sulphate sodium (at 5% in drinking water for 5 days) in a group of eight rats, whereas a matched control group received plain water. Activity and expression of matrix metalloproteinases were measured in colonic tissue homogenates using zymography and Western blot on days 3 and 5 after induction of colitis. In another set of experiments, two groups of colitic rats (20 per group) were treated with CGS-27023-A (20 mg/kg) or vehicle, respectively. On days 5 and 14, colonic mucosal lesions were blindly scored by microscopic examination. Induction of colitis led to a significant upregulation of matrix metalloproteinase-9 protein and its activity, but no change in matrix metalloproteinase-2 activity was observed. Treatment with CGS-27023-A significantly decreased the extent and severity of epithelial injury but did not influence mucosal repair. We conclude that increased activity of matrix metalloproteinases may contribute to epithelial damage in this model of colitis.
Medina
Carlos
C
Digestive Disease Research Unit, Hospital Vall d'Hebron, 08035 Barcelona, Spain.
Videla
Sebastián
S
Radomski
Anna
A
Radomski
Marek W
MW
Antolín
María
M
Guarner
Francisco
F
Vilaseca
Jaime
J
Salas
Antonio
A
Malagelada
Juan-R
JR
D000818:Animals; D000925:Anticoagulants; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000201:enzymology*; D016264:Dextran Sulfate; D003967:Diarrhea / Q000139:chemically induced / Q000378:metabolism; D004195:Disease Models, Animal; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000378:metabolism; D006877:Hydroxamic Acids; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology; D011719:Pyrazines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides
D000925:Anticoagulants; C097658:CGS 27023A; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011719:Pyrazines; D013449:Sulfonamides; D016264:Dextran Sulfate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9