Abstract
Pancreatic stellate cells (PSCs) play a key role in the development of pancreatic fibrosis, a pathological feature of chronic pancreatitis and pancreatic cancer. Here, we show that activation of rat PSCs in vitro is associated with increased expression of galectin-1 (gal-1) and that gal-1 modulates PSC function. Expression of the lectin was stimulated by fetal calf serum and platelet-derived growth factor. PSCs exposed to exogenous gal-1 proliferated at a higher rate and synthesised more collagen than controls. Gal-1-dependent collagen synthesis was blocked by lactose but not by cellobiose, suggesting that gal-1 acts on PSCs through targeting beta-galactoside-containing glycoconjugates. Analysis of gal-1 signalling in PSCs revealed an activation of the extracellular signal-regulated kinases 1 and 2 and enhanced DNA binding of AP-1 transcription factors. Together, our data implicate gal-1 in PSC activation and suggest further studies to analyse the role of endogenous lectins in the development of pancreatic fibrosis in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Animals
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Becaplermin
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Cell Proliferation / drug effects
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Cells, Cultured
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Collagen / biosynthesis
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Culture Media, Serum-Free / pharmacology
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Electrophoretic Mobility Shift Assay
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Galectin 1 / metabolism
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Galectin 1 / pharmacology
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Galectin 1 / physiology*
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Gene Expression / drug effects
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Gene Expression / genetics
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Male
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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NF-kappa B / metabolism
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Oligonucleotides / metabolism
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Pancreas / cytology*
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Phosphorylation / drug effects
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Platelet-Derived Growth Factor / pharmacology
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Proline / metabolism
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Promoter Regions, Genetic / genetics
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Protein Binding
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Proteins / pharmacology
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Proto-Oncogene Proteins c-sis
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Rats
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Rats, Inbred Lew
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Time Factors
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Transcription Factor AP-1 / metabolism
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Actins
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Culture Media, Serum-Free
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Galectin 1
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NF-kappa B
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Oligonucleotides
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Platelet-Derived Growth Factor
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Proteins
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Proto-Oncogene Proteins c-sis
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Transcription Factor AP-1
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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smooth muscle actin, rat
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Becaplermin
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Collagen
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Proline
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3