The Fibrosis of Chronic Pancreatitis: New Insights into the Role of Pancreatic Stellate Cells

Significance: Prominent fibrosis is a major histological feature of chronic pancreatitis, a progressive necroinflammatory condition of the pancreas, most commonly associated with alcohol abuse. Patients with this disease often develop exocrine and endocrine insufficiency characterized by maldigestion and diabetes. Up until just over a decade ago, there was little understanding of the pathogenesis of pancreatic fibrosis in chronic pancreatitis. Recent Advances: In recent times, significant progress has been made in this area, mostly due to the identification, isolation, and characterization of the cells, namely pancreatic stellate cells (PSCs) that are now established as key players in pancreatic fibrogenesis. In health, PSCs maintain normal tissue architecture via regulation of the synthesis and degradation of extracellular matrix (ECM) proteins. During pancreatic injury, PSCs transform into an activated phenotype that secretes excessive amounts of the ECM proteins that comprise fibrous tissue. Critical Issues: This Review summarizes current knowledge and critical aspects of PSC biology which have been increasingly well characterized over the past few years, particularly with respect to the response of PSCs to factors that stimulate or inhibit their activation and the intracellular signaling pathways governing these processes. Based on this knowledge, several therapeutic strategies have been examined in experimental models of pancreatic fibrosis, demonstrating that pancreatic fibrosis is a potentially reversible condition, at least in early stages. Future Directions: These will involve translation of the laboratory findings into effective clinical approaches to prevent/inhibit PSC activation so as to prevent, retard, or reverse the fibrotic process in pancreatitis. Antioxid. Redox Signal. 15, 2711-2722.