Mechanisms of pancreatic fibrosis

Pancreatic fibrosis, a characteristic histopathological feature of chronic pancreatitis, is no longer considered an epiphenomenon of chronic injury, but an active process that may be reversible in the early stages. The identification and characterization of pancreatic stellate cells (PSCs) in recent years has had a significant impact on research into pancreatic fibrogenesis. Accumulating evidence from both in vivo studies (using human pancreatic sections and experimental models of pancreatic fibrosis) and in vitro studies (using cultured pancreatic stellate cells) indicates a key role for activated PSCs in the fibrotic process. These cells are now known to be activated by ethanol and its metabolites and by several factors that are upregulated during pancreatic injury including growth factors, cytokines and oxidant stress. Based on this knowledge, potential antifibrotic strategies such as antioxidants and cytokine inhibition have been assessed in experimental models. Studies are also underway to characterise the signaling pathways/molecules responsible for mediating PSC activation, in order to identify potential therapeutic targets for the inhibition of PSC activation, thereby preventing or reversing the development of pancreatic fibrosis.