Synthesis and degradation of collagen in pancreatic fibrogenesis.
The mechanism of fibrogenesis in the pancreas is not well known. We analyzed the role of prolylhydroxylase and collagenase activities in the development of fibrosis in chronic alcoholic pancreatitis (CAP). Nineteen patients with CAP and 11 controls (organ donors) with normal pancreatic histology were included in the study. Pancreatic tissue was obtained from all subjects to measure (a) area of fibrosis (histomorphometric method); (b) prolylhydroxylase activity (PHase), which reflects the intracellular synthesis of collagen (Hutton's method); and (c) collagenase activity, which reflects the degradation of collagen (collagenase assay system, 3H). The percentage of the fibrosis area in relation to the total area of pancreatic tissue was significantly higher in CAP than in the control group (70.6+/-20.2% vs. 4.6+/-1.8%; p<0.001). Mean pancreatic PHase activity was also significantly higher in CAP than in the control group (775+/-258 cpm/mg protein/h vs. 405+/-151 cpm/mg protein/h; p<0.001). The collagenase activity was significantly lower in CAP than in the control group (8.7+/-3.5 cpm/cpm added/mg protein vs. 18.0+/-3.9 cpm/cpm added/mg protein; p<0.001). A significant correlation was observed between percentage fibrosis evaluated histomorphometrically and PHase activity in all patients (r = 0.72; p<0.001), and between PHase and collagenase activities in controls (r = 0.70; p = 0.024), but not in CAP. Pancreatic tissue in CAP has an increased fibrogenic activity and an impaired collagen-degradation capacity. These findings might explain the excessive development of fibrosis in CAP.
Valderrama
R
R
Institut de Malalties Digestives, Department of Medicine, Hospital Clínic, University of Barcelona, Spain.
Navarro
S
S
López
J M
JM
Caballería
J
J
Giménez
A
A
Parés
A
A
Adrián
M J
MJ
Fernández-Cruz
L
L
Terés
J
J
D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010180:Pancreatectomy; D019512:Pancreatitis, Alcoholic / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D011393:Procollagen-Proline Dioxygenase / Q000032:analysis; D012044:Regression Analysis
D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; D017364:Collagenases