Clusterin Expression in the Early Process of Pancreas Regeneration in the Pancreatectomized Rat

초록

We have previously reported up-regulation of clusterin at time of islet cell regeneration after beta cell injury. This led us to speculate that clusterin could be involved in the neogenic regeneration of the pancreas. We thus examined the expression of clusterin along the process of pancreatic regeneration in pancreatectomized rats. Clusterin and its mRNA increased significantly in the early phase of regeneration, particularly at 1-3 days after pancreatectomy. Clusterin was transiently expressed in the differentiating acinar cells, but faded afterwards. Interestingly these clusterin cells were negative for PCNA (proliferating cell nuclear antigen), while most epithelial cells in ductules in the regenerating tissue showed extensive proliferating activity. Clusterin expression was also detected in some endocrine cells of the regenerating tissue. Transfection of clusterin cDNA into primary cultured duct cells resulted in a 2.5 fold increase in cell proliferation, and induced transformation of non-differentiated duct cells into differentiated ones displaying cytokeratin immunoreactivity. Taken together, these results suggest that clusterin may play essential roles in the neogenic regeneration of pancreatic tissue by stimulating proliferation as well as differentiation of duct cells.