| PSP/reg inhibits cultured pancreatic stellate cell and regulates MMP/ TIMP ratio. | |
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MedLine Citation:
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PMID: 20860757 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. MATERIAL AND 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. |
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Authors:
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Ling Li; Daniel Bimmler; Rolf Graf; Shaoxia Zhou; Zilin Sun; Jinfei Chen; Marco Siech; Max G Bachem |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-23 |
Journal Detail:
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Title: European journal of clinical investigation Volume: 41 ISSN: 1365-2362 ISO Abbreviation: Eur. J. Clin. Invest. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0245331 Medline TA: Eur J Clin Invest Country: England |
Other Details:
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Languages: eng Pagination: 151-8 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation. |
Affiliation:
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Department of Clinical Chemistry, University Hospital Ulm, Ulm, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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