COMPARISON OF EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH FACTOR-BETA(1) EXPRESSION IN HORMONE-INDUCED ACUTE-PANCREATITIS IN RATS

Overexpression of transforming growth factors (TGF) in acute pancreati tis (AP) suggested that these substances play an important role in pan creatic repair and remodeling but the contribution of epidermal growth factor (EGF), that is well known to promote cell growth and regenerat ion, has not been investigated. The aim of this study was to compare t he gene and immunohistochemical expression of EGF and TGF-beta(1), cel l 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 caerul ein infusion. Pancreatic tissue DNA synthesis, cell proliferation, his tological and immunohistochemical assessments and plasma amylase were estimated following induction of AP. The mRNA expression for EGF and T GF-beta(1) was evaluated by reverse transcription-polymerase chain rea ction. During 10 days of the study after induction of AP a gradual nor malization of biochemical and histological parameters was observed. DN A synthesis and cell proliferation which were significantly decreased at 0 and 24 h, increased significantly at 48 and 72 h, and then gradua lly decreased reaching at day 10 the values similar to those of vehicl e-treated control rats. In these control rats the EGF mRNA or immunohi stochemical expression was not detected, while the TGF-beta(1) express ion 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-beta(1) showed a marked increase between 0 and 48 h and t hen again at day 10. We confirm that: (1) the expression of TGF-beta(1 ) during AP is biphasic with an initial increase probably related to p ancreatic damage and inhibition of cell proliferation and with the lat er phase of increase accompanied by the stimulation of the synthesis o f extracellular matrix components and (2) AP is accompanied by an indu ction of synthesis of EGF that occurs in the initial phase of AS, prob ably limiting the extent of AP, and enhancing the stimulation of the p ancreatic repair and regeneration.