Release of Hyaluronan and Laminin into Pancreatic Secretions

Abstract

Background: Development of fibrosis characterizes chronic pancreatitis. As it results from deposition of extracellular matrix (ECM) proteins such as hyaluronan (HA) or laminin, the release of these ECM components into blood or pancreatic secretion may be enhanced during the course of chronic pancreatitis. Patients, Material and Methods: Using immunoassays for HA and laminin, the concentration for these ECM components was measured in pancreatic juice and serum samples from 20 patients with and 20 patients without chronic pancreatitis. Pancreatic calculi of varying size and weight obtained from 13 patients with chronic pancreatitis were also examined for the content of ECM components. Tissue samples from normal pancreas and those showing chronic pancreatitis were investigated immunocytochemically with an antibody to HA synthetase (HAS). Results: After stimulation with secretin high levels of ECM components were found in the initial washout period in chronic pancreatitis patients as well as in controls. HA levels, however, were seen seven times higher in patients with chronic pancreatitis (mean ± SEM; 734 ± 301 vs. 95 ± 15 µg/l; p < 0.01). Serum HA levels correlated with the duration of chronic pancreatitis and with the levels of HA in pancreatic juice. HA and laminin were detected in the supernatants of pancreatic calculi (laminin 0.70 ± 0.30 U/l; HA 275 ± 85 µg/l). Immunocytochemically, strong staining for HAS was found in the duct epithelium and in centroacinar cells of chronic pancreatitis specimens. Conclusion: Demonstration of increased amounts of HA in pancreatic juice of chronic pancreatitis patients stimulated with secretin suggests enhanced production of this ECM component in the chronically inflamed pancreas. The source of HA appears to be the pancreatic ductal epithelium.

Coordinated Increase in Serum Platelet-Derived Growth Factor-BB and Transforming Growth Factor-β1 in Patients with Chronic Pancreatitis

“…Consistently, an increase in the extracellular matrix markers associated with the development of pancreatic fibrosis has also been reported [40]. These results are essentially similar to those reported previously [41].…”

COMP is Selectively Up-regulated in Degenerating Acinar Cells in Chronic Pancreatitis and in Chronic-Pancreatitis-like Lesions in Pancreatic Cancer

“…The destruction of the pancreatic parenchyma is accompanied by infiltrating inflammatory cells, followed by tissue remodeling, with ductal cell proliferation and ductular hyperplasia (1-3). Proliferation of the extracellular matrix (ECM) and increased deposition of interstitial ECM proteins (including collagens type I, III, and IV, laminin, fibronectin, and vitronectin) have been shown to be changes characteristic of CP (19)(20)(21). Interstitial collagens and fibronectin are increased and disorganized in both fibrous tissue and areas that appear histologically normal (22).…”

Vitamin E attenuates biochemical and morphological features associated with development of chronic pancreatitis

“…The soluble nonprotein component of the extracellular matrix (ECM) hyaluronic acid has been found to be a useful marker of fibrosis (16,33,39,48). Hyaluronic acid was measured in plasma as a collagen-independent marker of increased ECM turnover by means of a radiometric assay (Pharmacia HA test).…”