PMID- 19077460 OWN - NLM STAT- MEDLINE DCOM- 20090717 LR - 20181201 IS - 1424-3911 (Electronic) IS - 1424-3903 (Linking) VI - 9 IP - 1-2 DP - 2009 TI - Pancreatitis-associated protein inhibits human pancreatic stellate cell MMP-1 and -2, TIMP-1 and -2 secretion and RECK expression. PG - 99-110 LID - 10.1159/000178880 [doi] AB - 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. CI - Copyright 2008 S. Karger AG, Basel and IAP. FAU - Li, Ling AU - Li L AD - Department of Clinical Chemistry, University Hospital Ulm, Ulm, Germany. FAU - Bachem, Max G AU - Bachem MG FAU - Zhou, Shaoxia AU - Zhou S FAU - Sun, Zilin AU - Sun Z FAU - Chen, Jinfei AU - Chen J FAU - Siech, Marco AU - Siech M FAU - Bimmler, Daniel AU - Bimmler D FAU - Graf, Rolf AU - Graf R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081212 PL - Switzerland TA - Pancreatology JT - Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] JID - 100966936 RN - 0 (Antigens, Neoplasm) RN - 0 (Biomarkers, Tumor) RN - 0 (GPI-Linked Proteins) RN - 0 (Lectins, C-Type) RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (Membrane Glycoproteins) RN - 0 (Pancreatitis-Associated Proteins) RN - 0 (RECK protein, human) RN - 0 (REG3A protein, human) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Antigens, Neoplasm/*physiology MH - Biomarkers, Tumor/*physiology MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - GPI-Linked Proteins MH - Gene Expression/drug effects MH - Humans MH - Lectins, C-Type/*physiology MH - Matrix Metalloproteinase 1/metabolism MH - Matrix Metalloproteinase 2/metabolism MH - *Matrix Metalloproteinase Inhibitors MH - Membrane Glycoproteins/*biosynthesis MH - Pancreas/cytology/*drug effects MH - Pancreatitis-Associated Proteins MH - Tissue Inhibitor of Metalloproteinase-1/*antagonists & inhibitors/metabolism MH - Tissue Inhibitor of Metalloproteinase-2/*antagonists & inhibitors/metabolism EDAT- 2008/12/17 09:00 MHDA- 2009/07/18 09:00 CRDT- 2008/12/17 09:00 PHST- 2007/10/21 00:00 [received] PHST- 2008/03/21 00:00 [accepted] PHST- 2008/12/17 09:00 [entrez] PHST- 2008/12/17 09:00 [pubmed] PHST- 2009/07/18 09:00 [medline] AID - S1424-3903(09)80075-6 [pii] AID - 10.1159/000178880 [doi] PST - ppublish SO - Pancreatology. 2009;9(1-2):99-110. doi: 10.1159/000178880. Epub 2008 Dec 12.