NDT Advance Access originally published online on May 5, 2004
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Nephrol Dial Transplant (2004) 19: 1732-1741
Nephrol Dial Transplant Vol. 19 No. 7 © ERA-EDTA 2004; all rights reserved
Original Article
Activation of matrix metalloproteinase-2 causes peritoneal injury during peritoneal dialysis in rats
1 Terumo, R and D Center, Kanagawa and 2 Jichi Medical School, Department of Medicine, Tochigi, Japan
Correspondence and offprint requests to: Ichiro Hirahara, Terumo, R and D Center, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan. Email: Ichirou_Hirahara{at}terumo.co.jp
Background. Sclerosing peritonitis (SP) and encapsulating peritoneal sclerosis (EPS) are serious complications of continuous ambulatory peritoneal dialysis. Although we have shown previously that matrix metalloproteinase-2 (MMP-2) is increased in peritoneal injury leading to SP/EPS, most of the MMP-2 in the dialysate drained from the peritoneal cavity was the latent form that was lacking activity. In the present study, we investigated whether MMP-2 causes peritoneal injury.
Methods. To create an animal model of peritoneal injury, we administered intraperitoneally chlorhexidine gluconate to rats. Dialysate drained from these rats was analysed by gelatin zymography and MMP-2 activity was analysed by an in situ film zymography method. In vitro myofibroblasts were cultured in collagen three-dimensional culture and then MMP-2 in conditioned medium from the culture was analysed by gelatin zymography.
Results. Zymographic analysis revealed that latent form MMP-2 levels were high in the dialysate from peritoneal injury rats, whereas the active form was barely detectable. MMP-2 activity in the peritoneal tissue of the peritoneal injury rats was strongly detected by in situ film zymography. In vitro myofibroblasts were promoted to produce MMP-2 and to activate MMP-2 in collagen three-dimensional culture.
Conclusions. In the present model, most of the MMP-2 was in the latent form, but activation of MMP-2 was promoted in the peritoneum during peritoneal injury. Activated MMP-2 may be associated with the progression of peritoneal injury.
Keywords: matrix metalloproteinase-2; myofibroblasts; peritoneal injury; encapsulating peritoneal sclerosis; sclerosing peritonitis; peritoneal dialysis
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