Expression of transforming growth factor-beta 1 and epidermal growth factor in caerulein-induced pancreatitis in rat.
Growth factors such as TGF-beta 1 and EGF are known to modulate the deposition of extracellular matrix components and tissue repair and to affect the cellular growth but their expression in the course of pancreatitis has not been studied. In this study we investigated the gene expression of TGF-beta 1 mRNA and EGF mRNA and other parameters of the pancreas including DNA synthesis, blood flow (PBF), tissue protein content and plasma amylase during the induction of acute pancreatitis. Supramaximal dose of cearulein (10 mg/kg/h s.c.) was infused for 5 h to induce pancreatitis. Animals were killed after 1, 2, 3, 4 and 5 h of infusion. The PBF was measured, blood samples were withdrawn to determine serum amylase concentration, biopsy samples were taken to measure the protein content and DNA synthesis.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 synthesis accompanied by gradual decrease of PBF and significant increase in pancreatic weight. The pancreatic protein content and plasma amylase showed progressive rise during 5 h of cearulein infusion. Histology revealed tissue edema, cellular vacuolization and prominent leukocyte infiltration after 3 h of cearulein infusion. TGF-beta 1 mRNA was strongly expressed at each time interval beginning from the 1 h after the start of cearulein infusion. In contrast, EGF mRNA was detected only at 5 h after induction of pancreatitis. We conclude that 1) the development of caerulein-induced pancreatitis results in the inhibition of pancreatic growth and the reduction in PBF accompanied by enhanced expression of TGF-beta 1; 2) The expression of EGF that was observed at the end of the induction of pancreatitis may indicate the initiation of pancreatic repair; 3) TGF-beta 1 seems to lead to subsequent induction of EGF that may stimulate the regeneration of injured pancreas.
Konturek
P C
PC
Dept. Med. I., Univ. Erlangen-Nuremberg, Germany.
Dembiński
A
A
Warzecha
Z
Z
Ceranowicz
P
P
Konturek
S J
SJ
Stachura
J
J
Hahn
E G
EG
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000098:blood supply / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D017931:DNA Primers; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D012313:RNA; D002108:Ceruletide; D004247:DNA; D000681:Amylases