Effect of camostat mesilate on the expression of pancreatitis-associated protein (PAP), p8, and cytokines in rat spontaneous chronic pancreatitis.
An oral protease inhibitor, camostat mesilate (CM) has been used clinically for chronic pancreatitis (CP) in Japan, but it lacks enough scientific evidence of its effectiveness. The aim of this study was to analyze the effect of CM on the gene expressions of pancreatitis-associated protein (PAP), p8, and cytokines such as interleukin-6 and transforming growth factor-beta1 in spontaneous CP model (WBN/Kob rats). CM (10 mg/100 g body weight), mixed in MB-3 diet, was administered orally and gene expressions were analyzed by reverse transcription-polymerase chain reaction. In untreated WBN/Kob rats, the gene expressions of all the four factors peaked at 12 weeks, whereas they were significantly suppressed in the CM-treated rats. CM significantly increased the body weight and pancreatic wet weight, and it significantly inhibited inflammatory changes and fibrosis of the pancreas. These results suggest that CM inhibits pancreatic inflammation and fibrosis through the suppression of gene expressions of PAP, p8, and cytokines in CP.
Su
S B
SB
Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University, Japan.
Motoo
Y
Y
Iovanna
J L
JL
Xie
M J
MJ
Sawabu
N
N
D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D016207:Cytokines / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D015870:Gene Expression / Q000187:drug effects; D006133:Growth Substances / Q000235:genetics*; D006146:Guanidines / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics; D037181:Lectins, C-Type; D008297:Male; D009363:Neoplasm Proteins; D010195:Pancreatitis / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000073718:Pancreatitis-Associated Proteins; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics
D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D016207:Cytokines; D004268:DNA-Binding Proteins; D004952:Esters; D016670:Gabexate; D006133:Growth Substances; D006146:Guanidines; D015850:Interleukin-6; D037181:Lectins, C-Type; D009363:Neoplasm Proteins; D000073718:Pancreatitis-Associated Proteins; D016212:Transforming Growth Factor beta; C109741:Nupr1 protein, rat; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat; C034532:camostat