Coordinate regulation of PSP/reg and PAP isoforms as a family of secretory stress proteins in an animal model of chronic pancreatitis.
BACKGROUND
PSP/reg and PAP are secretory stress proteins (SSP) and may be part of a protective mechanism. They share structural homologies and form insoluble fibrils after tryptic activation. To further explore the regulation of these proteins, we investigated the male WBN/Kob rat, a model of pancreatic inflammatory and fibrotic disease similar to chronic pancreatitis.


METHODS
Expression of PSP/reg and PAP I, II and III in the WBN/Kob rat pancreas was evaluated on the mRNA and protein level, by immunohistochemistry and by highly sensitive isoform specific ELISAs.


RESULTS
The SSPs are constitutively secreted, PAP in nanomolar, PSP/reg in micromolar concentrations. Before conventional morphological changes are detectable in the WBN/Kob rat, focally increased expression of secretory stress protein is visible. SSP levels in pancreatic juice of WBN/Kob rats reach peak values 10- to 50-fold higher than in Wistar control rats. The highest expression was localized to acini with inflammatory infiltration.


CONCLUSIONS
There is a tight spatial and temporal association between pre-inflammatory changes or inflammation and SSP-expression. These results support our concept that PSP/reg and PAP are coordinately regulated SSP.
Bimmler
Daniel
D
Pancreatitis Research Laboratory, Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland. bda@chi.usz.ch
Schiesser
Marc
M
Perren
Aurel
A
Scheele
George
G
Angst
Eliane
E
Meili
Severin
S
Ammann
Rudolf
R
Graf
Rolf
R
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D051847:Lithostathine; D008297:Male; D009419:Nerve Tissue Proteins; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D000073718:Pancreatitis-Associated Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D037181:Lectins, C-Type; D051847:Lithostathine; D009419:Nerve Tissue Proteins; D000073718:Pancreatitis-Associated Proteins; D012333:RNA, Messenger; C497616:Reg1a protein, rat