Expression of vacuole membrane protein 1 (VMP1) in spontaneous chronic pancreatitis in the WBN/Kob rat.
OBJECTIVE
VMP1 is a stress-induced gene that is overexpressed in acute pancreatitis. Its overexpression promotes the formation of intracellular vacuoles and cell death. We investigated the expression of VMP1 mRNA and its relation to apoptosis in spontaneous chronic pancreatitis in the WBN/Kob rat.


METHODS
Four-week-old male WBN/Kob rats were fed a special breeding diet, MB-3, for 20 weeks. Rats were killed every 4 weeks, and the pancreas was examined. VMP1 mRNA expression was determined by reverse transcriptase polymerase chain reaction with a semiquantitative analysis, direct sequencing, and in situ hybridization. Immunohistochemistry for proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) were used to detect cell proliferation and apoptosis, respectively.


RESULTS
Vacuolar formation was most prominent at 12 weeks, when chronic pancreatitis occurred. VMP1 mRNA was also strongly expressed at 12 weeks. In situ hybridization revealed VMP1 mRNA was expressed in acinar cells. Apoptosis was increased at 12 and 20 weeks, and PCNA expression was strongest at 16 weeks in the course of chronic pancreatitis.


CONCLUSIONS
VMP1 mRNA expression paralleled the formation of vacuoles and apoptosis in acinar cells in the course of chronic pancreatitis in WBN/Kob rats.
Jiang
Pei-Hong
PH
Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Motoo
Yoshiharu
Y
Vaccaro
María Inés
MI
Iovanna
Juan Lucio
JL
Okada
Gensaku
G
Sawabu
Norio
N
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002908:Chronic Disease; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014617:Vacuoles / Q000378:metabolism
D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; C446296:VMP1 protein, rat