title: PSP/reg inhibits cultured pancreatic stellate cell and regulates MMP/ TIMP ratio.
abstract: BACKGROUND
  Pancreatic stellate cells (PSC) play a central role in fibrogenesis associated with acute and chronic pancreatitis. Pancreatic stone protein/regenerating protein (PSP/reg) belongs to a family of secretory stress proteins (SSP) that are constitutively synthesized by pancreatic acinar cells and upregulated dramatically during acute and chronic pancreatitis. Assuming a protective role of this stress protein, we investigated its effects on human PSC.
  
  
  METHODS
  Pancreatic stellate cells were obtained by outgrowth from fibrotic human pancreas tissue. PSP/reg was expressed in the yeast Pichia pastoris and purified from medium supernatants. PSP/reg was added at concentrations of 100 ng/mL to cultured PSC. Cell proliferation was determined by bromodeoxyuridine incorporation. PSC migration was assessed by a wound healing assay. Extracellular matrix (collagen type I and fibronectin), matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) were demonstrated on protein level.
  
  
  RESULTS
  Pancreatic stone protein/regenerating protein inhibited PSC proliferation and migration. Soluble collagen I and fibronectin were reduced after the addition of PSP/reg. PSP/reg slightly decreased the synthesis of MMP-1 and MMP-2 and strongly decreased TIMP-1 and TIMP-2 concentrations in PSC supernatants.
  
  
  CONCLUSIONS
  Our work describes a novel aspect that in vitro PSP/reg reduces PSC activity (proliferation and migration) and stimulates fibrolysis by increasing MMP/TIMP ratio. The findings suggest that PSP/reg might have a protective function in the repair phase of acute and chronic pancreatitis by promoting resolution of fibrosis. We highlight PSP/reg as an antifibrogenic protein in pancreatic injury.
authors.affiliation: Department of Clinical Chemistry, University Hospital Ulm, Ulm, Germany.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Daniel
authors.initials: D
authors.lastname: Bimmler
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Zhou
authors.forename: Zilin
authors.initials: Z
authors.lastname: Sun
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
authors.forename: Marco
authors.initials: M
authors.lastname: Siech
authors.forename: Max G
authors.initials: MG
authors.lastname: Bachem
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051847:Lithostathine / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D058954:Pancreatic Stellate Cells / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
chemical_list: D051847:Lithostathine; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases