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.
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 injuryrats, whereas the active form was barely detectable. MMP-2 activity in the peritoneal tissue of the peritoneal injuryrats 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.
Authors: Yeoungjee Cho; David W Johnson; David A Vesey; Carmel M Hawley; Elaine M Pascoe; Margaret Clarke; Nicholas Topley Journal: Perit Dial Int Date: 2014-10-07 Impact factor: 1.756