Pancreatitis-Associated Protein Inhibits Human Pancreatic Stellate Cell MMP-1 and -2, TIMP-1 and -2 Secretion and RECK Expression |
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| Authors: | Ling Li Max G Bachem Shaoxia Zhou Zilin Sun Jinfei Chen Marco Siech Daniel Bimmler Rolf Graf |
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| Institution: | 1. Howard Hughes Medical Institute, USA;2. Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA;3. Joslin Diabetes Center, Boston, MA 02215, USA;4. Harvard Medical School, Boston, MA 02215, USA;5. Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia;6. Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia;7. Department of Haematology, Cambridge Institute for Medical Research University of Cambridge, Cambridge CB2 0XY, UK;8. Wellcome Trust — Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0XY, UK;9. Division of Newborn Medicine, Boston Children''s Hospital, Harvard Medical School, MA, USA;1. Institute of Pathology, Technische Universität München, Munich, Germany;2. Institute for Experimental Oncology and Therapy Research, Technische Universität München, Munich, Germany;3. Department of Surgery, Technische Universität München, Munich, Germany;4. Research Unit Analytical Pathology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany;5. Pathology, Kantonspital Münsterlingen, Münsterlingen, Switzerland;6. Department of Surgery, Koc University School of Medicine, Istanbul, Turkey |
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| Abstract: | 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 pancreastissue. 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 cysteinerich 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. |
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