Tumor Protein p53-Induced Nuclear Protein 1 (TP53INP1) in Spontaneous Chronic Pancreatitis in the WBN/Kob Rat: Drug Effects on Its Expression in the Pancreas

(Journal Article): Tumor Protein p53-Induced Nuclear Protein 1 (TP53INP1) in Spontaneous Chronic Pancreatitis in the WBN/Kob Rat: Drug Effects on Its Expression in the Pancreas

Jiang PH, Motoo Y, Iovanna JL, Pébusque MJ, Xie MJ, Okada G, Sawabu N (Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University. Kanazawa, Japan, motoo@kenroku.kanazawa-u.ac.jp )

IN: JOP. J Pancreas (Online) 2004; 05(4):205-216

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ABSTRACT: CONTEXT: The tumor protein p53-induced nuclear protein 1 (TP53INP1) gene was found using DNA microarray technology as an overexpressed gene in acute pancreatitis. However, expression of TP53INP1 in chronic pancreatitis has not been previously reported. OBJECTIVE: This study investigated TP53INP1 gene expression and its relationship with p53 and apoptosis in spontaneous chronic pancreatitis in the Wistar-Bonn/Kobori rat. METHODS: Ninety four-week-old male Wistar-Bonn/Kobori rats were fed a special breeding diet until sacrifice. Camostat mesilate (n=30) or a herbal medicine (Saiko-keishi-to; n=30) were mixed with the diet, while the other 30 rats were untreated. The rats were sacrificed every 4 weeks for 20 weeks, and the pancreas was examined. In addition, 6 four-week-old male Wistar-Bonn/Kobori rats were sacrificed and studied as starting reference. Finally, Wistar rats (n=36) were studied as controls. MAIN OUTCOME MEASURE: TP53INP1 mRNA expression was determined by reverse transcription-polymerase chain reaction using semi-quantitative analysis, direct sequencing and in situ hybridization. RESULTS: TP53INP1 mRNA was strongly expressed at 12 weeks when chronic pancreatitis developed, with a second peak at 20 weeks. The expression kinetics of TP53INP1 mRNA paralleled acinar cell apoptosis assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The p53 mRNA expression showed a single peak at 12 weeks. In situ hybridization revealed that TP53INP1 mRNA was expressed mainly in acinar cells. Therapeutic drugs such as camostat mesilate and a herbal medicine Saiko-keishi-to suppressed the TP53INP1 mRNA expression. TP53INP1 mRNA induction in acinar cells was confirmed with in vitro experiments using an arginine-induced rat pancreatic acinar AR4-2J cell injury model. CONCLUSIONS: TP53INP1 expression may reflect the acute-phase response and apoptosis of acinar cells in the course of chronic pancreatitis.

TYPE OF PUBLICATION: Original Article

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