Pancreatitis-associated protein inhibits human pancreatic stellate cell MMP-1 and -2, TIMP-1 and -2 secretion and RECK expression

Pancreatology. 2009;9(1-2):99-110. doi: 10.1159/000178880. Epub 2008 Dec 12.


Background/aims: Pancreatic stellate cells (PSCs) play a key role in fibrogenesis associated with acute and chronic pancreatitis. Pancreatitis-associated protein (PAP), an acute-phase protein, is dramatically upregulated during acute and chronic pancreatitis. Assuming a protective role of PAP, we investigated its effects on human PSCs.

Methods: PSCs were obtained by outgrowth from fibrotic human pancreas tissue. PAP was expressed in the yeast Pichia pastoris. PAP was added at 10 ng/ml to cultured PSCs. Cell proliferation was determined by bromodeoxyuridine incorporation. PSC migration was assessed by a wound healing assay. Collagen types I and III, fibronectin, matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) were demonstrated on protein and mRNA level.

Results: PAP had no significant effect on PSC proliferation and migration. Cell-associated fibrillar collagen types I and III and fibronectin increased after addition of PAP to PSCs. PAP diminished the expression of MMP-1 and -2 and TIMP-1 and -2 and their concentrations in PSC supernatants. RECK was detected on the surface of PSCs and its expression was reduced after PAP application.

Conclusions: Our data offer new insights into the biological functions of PAP, which may play an important role in wound healing response and cell-matrix interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / physiology*
  • Biomarkers, Tumor / physiology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • GPI-Linked Proteins
  • Gene Expression / drug effects
  • Humans
  • Lectins, C-Type / physiology*
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Membrane Glycoproteins / biosynthesis*
  • Pancreas / cytology
  • Pancreas / drug effects*
  • Pancreatitis-Associated Proteins
  • Tissue Inhibitor of Metalloproteinase-1 / antagonists & inhibitors*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • Lectins, C-Type
  • Matrix Metalloproteinase Inhibitors
  • Membrane Glycoproteins
  • Pancreatitis-Associated Proteins
  • RECK protein, human
  • REG3A protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 1