Comparison of epidermal growth factor and transforming growth factor-beta1 expression in hormone-induced acute pancreatitis in rats.
Overexpression of transforming growth factors (TGF) in acute pancreatitis (AP) suggested that these substances play an important role in pancreatic repair and remodeling but the contribution of epidermal growth factor (EGF), that is well known to promote cell growth and regeneration, has not been investigated. The aim of this study was to compare the gene and immunohistochemical expression of EGF and TGF-beta1, cell proliferation, and biochemical parameters in AP induced by infusion of a supramaximal dose of caerulein in rats. The rats were sacrificed at 0, 12, 24, 48, 72 h, 5 and 10 days after the termination of caerulein infusion. Pancreatic tissue DNA synthesis, cell proliferation, histological and immunohistochemical assessments and plasma amylase were estimated following induction of AP. The mRNA expression for EGF and TGF-beta1 was evaluated by reverse transcription-polymerase chain reaction. During 10 days of the study after induction of AP a gradual normalization of biochemical and histological parameters was observed. DNA synthesis and cell proliferation which were significantly decreased at 0 and 24 h, increased significantly at 48 and 72 h, and then gradually decreased reaching at day 10 the values similar to those of vehicle-treated control rats. In these control rats the EGF mRNA or immunohistochemical expression was not detected, while the TGF-beta1 expression was weak. After induction of AP, the mRNA and immunohistochemical expression of EGF showed an increase during the initial 5 days, while those of TGF-beta1 showed a marked increase between 0 and 48 h and then again at day 10. We confirm that: (1) the expression of TGF-beta1 during AP is biphasic with an initial increase probably related to pancreatic damage and inhibition of cell proliferation and with the later phase of increase accompanied by the stimulation of the synthesis of extracellular matrix components and (2) AP is accompanied by an induction of synthesis of EGF that occurs in the initial phase of AP, probably limiting the extent of AP, and enhancing the stimulation of the pancreatic repair and regeneration.
Konturek
P C
PC
Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany.
Dembinski
A
A
Warzecha
Z
Z
Ihlm
A
A
Ceranowicz
P
P
Konturek
S J
SJ
Stachura
J
J
Hahn
E G
EG
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002108:Ceruletide; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D005765:Gastrointestinal Agents; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000187:drug effects / Q000235:genetics
D015415:Biomarkers; D005765:Gastrointestinal Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D002108:Ceruletide; D004247:DNA