Hepatocyte growth factor and fibroblast growth factor 2 are overexpressed after cerulein-induced acute pancreatitis

The regenerative process after acute inflammation of the pancreas is charac terized by cell proliferation as well as synthesis and transient deposition of extracellular matrix. Although the regulation of these processes is sti ll unknown, there is growing evidence that the coordinated activity of vari ous growth factors plays an important role in regeneration. Cerulein-induce d pancreatitis in the rat was used to analyze whether growth factors and th eir receptor concentrations are changed in the acute pancreatitis. Messenge r RNA hybridization revealed an individual expression pattern for each anal yzed growth factor. The mRNA levels of platelet-derived growth factor B (PD GF B), epidermal growth factor (EGF), and insulin-like growth factor 2 (IGF -2) were not altered, whereas fibroblast growth factor-1 (FGF-1) and 2, IGF -1, transforming growth factor-alpha (TGF alpha), and hepatocyte growth fac tor (HGF) showed markedly increased concentrations with different expressio n maxima and duration compared with mRNA levels in healthy pancreata. The F GF-2 and IGF-1 expressions were increased between 1 and 3 days after induct ion of pancreatitis with maxima at day 2. HGF and FGF-1 mRNAs were upregula ted between days 3 and 5. In contrast, TGF alpha exhibited the most prolong ed overexpression. In the corresponding receptors, only c-met, the HGF-bind ing protein, showed higher mRNA and protein levels, whereas the expression of the other receptors did not change. Furthermore, in cultured pancreatic epithelial cells, HGF stimulated the expression of its own receptor in an a utocrine manner. These results point out that the highly coordinated proces s of regeneration after pancreatitis may be influenced by a sequential indu ction and expression of peptide growth factors and their receptors.