Increased expression of transforming growth factor βs after acute oedematous pancreatitis in rats suggests a role in pancreatic repair

Abstract

Background - Transforming growth factor β isoforms (TGFβs) belong to a family of multifunctional regulators of cellular growth and differentiation. They are mitogenic and chemotactic for fibroblasts and are potent stimulators of extracellular matrix production (collagen) and deposition. Upregulation of TGFβ transcription has been reported for several in vivo systems during repair after injury. Aims - To study the expression of the three mammalian isoforms of TGFβ (TGFβ1-3) and their relation to collagen expression as a marker for fibroblast response in acute oedematous pancreatitis in rats. Methods - Using northern blot analysis and immunohistochemistry, the expression and localisation of TGFβ isoforms, collagen, and amylase were analysed during the course of acute oedematous pancreatitis in rats, experimentally induced by intravenous caerulein infusion. Results - Induction of acute pancreatitis resulted in a biphasic peak pattern of expression of TGFβ1, β2, and β3 mRNA, with a pronounced increase from day 1 to day 3 (sixfold, 2.5-fold, fivefold, respectively) and again from day 5 to day 7 (threefold, 2.3-fold, 3.5-fold, respectively). The temporal changes in TGFβ mRNA identically paralleled the expression in collagen mRNA. In contrast, amylase mRNA expression, used as a general indicator of acinar cell integrity, was slightly decreased after induction of acute pancreatitis. Immunohistochemical analysis of pancreatitis tissue showed that increased expression of TGFβs was mainly present in the pancreatic acinar and ductal cells; this was evident within one day after pancreatitis induction. Conclusion - Overexpression of TGFβs after induction of acute pancreatitis suggests a role for these proteins in pancreatic repair and remodelling. The increased levels of TGFβs may help suppress immune activation, and may contribute to the increase in the extracellular matrix including collagen and to the repair of the pancreatic parenchyma.