Decreased type IV collagenase activity in experimental pancreatic fibrosis

Background. Severe hyperstimulation and duct obstruction pancreatitis (SHOP ) is characterized by pancreatic fibrosis and loss of acinar cell mass. MMP -2 and MMP-9 are type IV collagenases and gelatinases, We hypothesized that fibrosis results from disruption of the normal collagen homeostasis and th at altered activity of the type IV collagenases may contribute to pancreati c fibrosis in SHOP. Methods, SHOP rats (n = 15) were prepared with pancreatic duct obstruction and cerulein (50 mug/kg/d, ip) hyperstimulation. Pancreas from unoperated c ontrol (n = 8), 48 h SHOP (n = 8), and 96 h SHOP (n = 7) rats was harvested , homogenized, and assayed for protein concentration (BCA method). Type TV collagenase (MMP-2 and MMP-9) expression was measured by zymography using g elatin as substrate. Type IV collagenase activity was quantified with a flu orescence assay. Results. Expression of the active form of MMP-9 decreased while latent MMP- 9 and active and latent MMP-2 increased on gelatin zymography, Activity of type Pr collagenases (MMP-2 and MMP-9) progressively decreases with SHOP in jury, The differences between expression and activity are likely due to pos ttranslational regulators such as MT-MMPs and TIMPs, Conclusions. Collagenase expression and activity are decreased in the SHOP model of pancreatitis, suggesting a decrease in the homeostatic mechanisms for type IV collagen in the extracellular matrix. Therefore, early fibrosis in the SHOP model is, at least in part, due to alterations in collagen hom eostasis and not simply increased collagen production. (C) 2001 Academic Pr ess.