Crucial role of fibrogenesis in pancreatic diseases

Chronic pancreatitis and pancreatic cancer are characterised by a progressive fibrosis. Accumulation of extracellular matrix not only accompanies both diseases but is directly involved in their progression, suggesting inhibition of fibrogenesis as a potential therapeutic strategy. Pancreatic stellate cells (PSC) are the main extracellular matrix-producing cell type in the diseased pancreas. In response to pro-fibrogenic mediators including cytokines and ethanol metabolites, PSC undergo phenotypic changes termed activation, resulting in the exhibition of a myofibroblast-like phenotype. In the perpetuation of PSC activation, autocrine loops of mediators such as transforming growth factor beta play an important role. Most recently signal transduction pathways in PSC that are associated with the process of activation were characterised, facilitating identification of potential intracellular targets for an anti-fibrotic therapy. While some putative inhibitors of fibrogenesis have been tested in animal models of pancreatic fibrosis for their in vivo efficiency, clinical studies still remain to be performed.