Chronic pancreatitis pathogenesis, toxic-metabolic agents, oxidative stress, obstruction, recurrent and severe acute pancreatitis (necrosis-fibrosis), autoimmune and genetic factors, and mechanisms of chronic pancreatitis remain under investigation. Chronic pancreatitis is histologically characterized by progressive, dense irregular fibrosis with destruction and loss of the exocrine parenchyma. Fibrosis is a potentially reversible condition in early stages. In recent years, the identification and characterization of pancreatic stellate cells (PSCs) indicate a key role for activated PSCs in the early stages of fibrogenesis. The role of PSCs has been examined in vivo (using pancreatic tissue from animal models of experimental pancreatitis) and in vitro (using PSCs in culture). The reversibility of fibrosis in ethionine-induced pancreatitis in dogs has been observed in the early stages. Activated PSCs, a-SMA-positive cells morphologically produce and secret extracellular matrix proteins, colagen and fibronectin. It is likely that dense and irreversible fibrosis in chronic pancreatitis was formed after recurrent and severe pancreatic injury.
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Chronic pancreatitis is histologically characterized by dense irregular fibrosis with destruction and loss of the exocrine parenchyma. It is not known whether the progression of fibrosis occurs from acute to chronic pancreatitis. Neither is it known whether destruction and loss of the exocrine parenchyma induce pancreatic fibrosis. Prominent theories of chronic pancreatitis pathogenesis, the toxic-metabolic theory, the oxidative stress hypothesis, the stone-and-duct-obstruction theory and the necrosis-fibrosis hypothesis are known. Experimental duct ligation and ethanol feeding induce collagen synthesis in the rat pancreas [1, 2]. Ethanol feeding induces metabolic disturbance in pancreatic exocrine parenchyma. However, experimental fibrosis in the pancreas of small animals such as rats probably decreases after such injuries. After injury, the rat pancreas regenerates with a decrease and resolution of fibrous deposition. It is difficult to experimentally induce dense fibrosis in the rat pancreas. Recently, activated pancreatic stellate cells (PSCs) have been implicated in the pathogenesis of pancreatic fibrosis and inflammation [3-5]. PSCs are located in interlobular areas and periacinar spaces of the rat pancreas. PSCs (also known as vitamin A-storing cells) were first described in the pancreas of mice given vitamin A by Watari et al. in 1982 . These cells were identified by electron microscopy in normal rat and human pancreatic tissues , and are morphologically similar to the hepatic stellate cells (HSCs) that play a central role in the inflammation and fibrogenesis of the liver. HSCs, also called vitamin A-storing cells, Ito cells, or fat-storing cells, are predominantly located in the space of Disse . During liver fibrogenesis, HSCs are activated and transformed into myofibroblasts. There is increasing evidence demonstrating a central role for PSCs in pancreatic fibrogenesis. PSCs are identified using antibodies to desmin and glial acidic protein (GFAP) . During pancreatic injury PSCs are activated and transformed into myofibroblasts in a manner similar to HSCs. Activated PSCs expressing smooth muscle actin (SMA) produce and secrete the extracellular matrix proteins, collagen, fibronectin and laminin . Cytokines such as transforming growth factor-p and platelet derived growth factor mediate activation of PSCs. These cytokines are produced and secreted by parenchymal cells, inflammatory cells, and PSCs. PSC activation occurs in fibrotic areas of pancreatic tissue from patients with chronic pancreatitis and from experimental animal models .
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