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 β 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.