Coordinate regulation of PSP/reg and PAP isoforms as a family of secretory stress proteins in an animal model of chronic pancreatitis

J Surg Res. 2004 May 15;118(2):122-35. doi: 10.1016/S0022-4804(03)00342-1.

Abstract

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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Chronic Disease
  • Disease Models, Animal
  • Disease Progression
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Lithostathine
  • Male
  • Nerve Tissue Proteins*
  • Pancreatitis / metabolism*
  • Pancreatitis / pathology
  • Pancreatitis / physiopathology*
  • Pancreatitis-Associated Proteins
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar

Substances

  • Acute-Phase Proteins
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Lectins, C-Type
  • Lithostathine
  • Nerve Tissue Proteins
  • Pancreatitis-Associated Proteins
  • RNA, Messenger
  • Reg1a protein, rat