EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND EPIDERMAL GROWTH-FACTOR IN CERULEIN-INDUCED PANCREATITIS IN RAT

Growth factors such as TGF-beta 1 and EGF are known to modulate the de position of extracellular matrix components and tissue repair and io a ffect the cellular growth but their expression in the course of pancre atitis has not been studied. In this study we investigated the gene ex pression of TGF-beta 1 mRNA and EGF mRNA and other parameters of the p ancreas including DNA synthesis, blood flow (PBF), tissue protein cont ent and plasma amylase during the induction of acute pancreatitis. Sup ramaximal dose of cearulein (10 mg/kg/h s.c.) was infused for 5 h to i nduce pancreatitis. Animals were killed after 1, 2, 3, 4 and 5 h of in fusion. The PBF was measured, blood samples were withdrawn to determin e serum amylase concentration, biopsy samples were taken to measure th e protein content and DNA synthesis. Expression of TGF-beta 1 and EGF mRNA was studied by reverse-transcription of polymerase chain reaction (RT-PCR). Caerulein infused caused a time-dependent decrease in DNA s ynthesis accompanied by gradual decrease of PBF and significant increa se in pancreatic weight. The pancreatic protein content and plasma amy lase showed progressive rise during 5 h of cearulein infusion. Histolo gy revealed tissue edema, cellular vacuolization and prominent leukocy te infiltration after 3 h of cearulein infusion. TGF-beta 1 mRNA was s trongly expressed at each time interval beginning from the 1 h after t he start of cearulein infusion. In contrast, EGF mRNA was detected onl y at 5 h after induction of pancreatitis. We conclude that 1) the deve lopment of caerulein-induced pancreatitis results in the inhibition of pancreatic growth and the reduction in PBF accompanied by enhanced ex pression of TGF-beta 1; 2) The expression of EGF that was observed at the end of the induction of pancreatitis may indicate the initiation o f pancreatic repair; 3) TGF-beta 1 seems to lead to subsequent inducti on of EGF that may stimulate the regeneration of injured pancreas.