November 3 (Thu.), 14:00–17:00, Room 8 (Portopia Hotel Main Building Kairaku 2)
IS-W1-2_G
Reduced E-cadherin expression may cause destruction of pancreatic parenchyma in chronic pancreatitis.
T. Sato1
Co-authors: W. Shibata2, S. Maeda1
1
Department of Gastroenterology, Yokohama City University Graduate School of Medicine
2
Advanced Medical Research Center, Yokohama City University
Aim : E-cadherin(CDH1)-mediated cell-cell junctions play important roles in the maintenance of tissue structure in multiple organisms. This study aimed to clarify the role of CDH1 in chronic pancreatitis. Methods: We used chronic pancreatitis tissue array for immunohistochemical analysis of CDH1. Pancreas-specific conditional CDH1 knockout mice were generated by crossing Ptf1a-cre mice with CDH1F/F mice (CDH1δpanc), and CDH1F/F mice were used as controls. Mice were sacrificed at postnatal day 0 (P0), 2, 6, 12, and 15 to obtain pancreatic tissues, and were analyzed by hematoxylin and eosin, and immunohistochemical staining. Serum amylase levels in these mice were also evaluated. Results: CDH1 expression was negative or weak in 17 cases (43%) in the tissue array. Loss of CDH1 expression resulted in no morphological change at P0 and P2, but it caused drastic change at P6, 12, and 15. We observed infiltration of CD45 positive cells and structural destruction accompanied by acinar-to-ductal metaplasia, decreased amylase positive cells, increased cleaved caspase3-positive apoptotic cells, and wide range of fibrosis. All mice died around P18 probably due to loss of pancreatic function, resembling human chronic pancreatitis. Serum amylase levels were elevated in CDH1δpanc mice compared with the controls. Conclusion: Reduced CDH1 expression could cause the structural destruction of pancreas parenchyma, and might accelerate the chronic pancreatitis.