Abstract
OBJECTIVES: Alcohol abuse is one of the most common factors associated with acute and chronic pancreatitis. Although it is evident that alcohol abuse can have an important role in the development of pancreatitis, it does not seem that alcohol abuse alone is responsible for this disease. We investigated the involvement of ethanol in the impairment of pancreatic repair after induction of pancreatitis. METHODS: A biologically relevant mouse model of alcoholic pancreatitis, combining long-term ethanol consumption and coxsackievirus infection, was used to investigate the effects of ethanol on pancreatic regeneration. Tissues were harvested and analyzed by reverse transcription-polymerase chain reaction and immunoblot. RESULTS: These studies demonstrate that long-term ethanol consumption impairs the structural repair of the exocrine pancreas. This is accompanied by a delay in the restitution of lipase expression. In addition, impaired expression of the critical pancreatic transcription factors, PDX1 and PTF1, and the mediator of Notch signaling, HES1, was observed. CONCLUSIONS: Long-term ethanol consumption impairs the structural repair and functional restitution of the pancreas after severe injury. These impairments may, in part, be explained by the impaired expression of factors important in the development and maintenance of the exocrine pancreas. Impaired pancreatic regeneration may have a role in the pathogenesis of alcoholic pancreatitis.