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Journal of Histochemistry and Cytochemistry, Vol. 51, 1355-1365, October 2003, Copyright © 2003, The Histochemical Society, Inc.

ARTICLE

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

Bon-Hong Mina, Byeong-Moo Kimb, Seung-Hee Leeb, Sang-Wook Kanga, Moise Bendayanc, and In-Sun Parkb
a Department of Pharmacology and BK21 Program for Medical Sciences, College of Medicine, Korea University, Seoul, Korea
b Department of Anatomy, College of Medicine, Inha University, Incheon, Korea
c Department of Pathology and Cell Biology, Faculty of Medicine, University of Montreal, Quebec, Canada

Correspondence to: In-Sun Park, Dept. of Anatomy, College of Medicine, Inha University, Choong-Gu, Shinheung-Dong, Inchon 400-103, Korea. E-mail: sunpark@inha.ac.kr

We have previously reported upregulation of clusterin at the time of islet cell regeneration after ß-cell injury. This led us to speculate that clusterin might be involved in the neogenic regeneration of the pancreas. Clusterin expression was examined throughout the process of pancreatic neogenesis in pancreatectomized rats. For in vitro analysis, duct cells were isolated from the rat pancreas and clusterin cDNA was transfected for its overexpression. 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), whereas most epithelial cells in ductules in the regenerating tissue showed extensive proliferative 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 cells displaying cytokeratin immunoreactivity. Taken together, these results suggest that clusterin may play essential roles in the neogenic regeneration of pancreatic tissue by stimulating proliferation and differentiation of duct cells. (J Histochem Cytochem 51:1355–1365, 2003)

Key Words: clusterin, duct cell, islet cell, proliferation, differentiation, pancreatectomy, diabetes


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