Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis.
Over a decade, there is accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in the development of pancreatic fibrosis. In response to pancreatic injury or inflammation, quiescent PSCs are transformed (activated) to myofibroblast-like cells, which express alpha-smooth muscle actin. Activated PSCs proliferate, migrate, produce extracellular matrix components, such as type I collagen, and express cytokines and chemokines. Recent studies have suggested novel roles of PSCs in local immune functions and angiogenesis in the pancreas. If the pancreatic inflammation and injury are sustained or repeated, PSC activation is perpetuated, leading to the development of pancreatic fibrosis. In this context, pancreatic fibrosis can be defined as pathologic changes of extracellular matrix composition in both quantity and quality, resulting from perpetuated activation of PSCs. Because PSCs are very similar to hepatic stellate cells, PSC research should develop in directions more relevant to the pathophysiology of the pancreas, for example, issues related to trypsin, non-oxidative alcohol metabolites, and pancreatic cancer. Indeed, in addition to their roles in chronic pancreatitis, it has been increasingly recognized that PSCs contribute to the progression of pancreatic cancer. Very recently, contribution of bone marrow-derived cells to PSCs was reported. Further elucidation of the roles of PSCs in pancreatic fibrosis should promote development of rational approaches for the treatment of chronic pancreatitis and pancreatic cancer.
Masamune
Atsushi
A
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan. amasamune@m.tains.tohoku.ac.jp
Watanabe
Takashi
T
Kikuta
Kazuhiro
K
Shimosegawa
Tooru
T
D000818:Animals; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D051379:Mice; D008954:Models, Biological; D010179:Pancreas / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000150:complications / Q000473:pathology*