Galectin-1 is an inductor of pancreatic stellate cell activation

Cell Signal. 2005 Oct;17(10):1240-7. doi: 10.1016/j.cellsig.2004.12.012. Epub 2005 Jan 21.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Becaplermin
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Collagen / biosynthesis
  • Culture Media, Serum-Free / pharmacology
  • Electrophoretic Mobility Shift Assay
  • Galectin 1 / metabolism
  • Galectin 1 / pharmacology
  • Galectin 1 / physiology*
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NF-kappa B / metabolism
  • Oligonucleotides / metabolism
  • Pancreas / cytology*
  • Phosphorylation / drug effects
  • Platelet-Derived Growth Factor / pharmacology
  • Proline / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Proteins / pharmacology
  • Proto-Oncogene Proteins c-sis
  • Rats
  • Rats, Inbred Lew
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Time Factors
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Actins
  • Culture Media, Serum-Free
  • Galectin 1
  • NF-kappa B
  • Oligonucleotides
  • Platelet-Derived Growth Factor
  • Proteins
  • Proto-Oncogene Proteins c-sis
  • Transcription Factor AP-1
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • smooth muscle actin, rat
  • Becaplermin
  • Collagen
  • Proline
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3