Galectin-1 expression in activated pancreatic satellite cells promotes fibrosis in chronic pancreatitis/pancreatic cancer via the TGF-β1/Smad pathway

Oncol Rep. 2018 Mar;39(3):1347-1355. doi: 10.3892/or.2018.6202. Epub 2018 Jan 9.

Abstract

Chronic pancreatitis/pancreatic cancer (CP/PC) is characterized by fibrous connective tissue proliferation induced by activated pancreatic stellate cells (PSCs). Galectin-1 is upregulated in activated PSCs and is important for the continuing activation of PSCs. The aim of this study was to evaluate the effect of galectin-1 derived from activated PSCs on the progression of fibrosis in CP/PC. To this end, the expression of desmin, α-SMA, galectin-1, fibronectin and collagen type I in normal pancreatic, CP and PC tissues, as well as quiescent/activated PSCs, was investigated. The proliferation rate and migration ability of control, galectin-1-overexpressing and galectin-1-silenced PSCs were also evaluated, as well as the mRNA and protein expression of fibronectin, collagen type I, α-SMA, tissue inhibitors of metalloproteinases (TIMP)-1, MMP-2, Smad2 and TGF-β1. Furthermore, the effect of adding a TGF-β1 receptor inhibitor on the expression of these proteins was examined. The results revealed that the expression profile of desmin, α-SMA, galectin-1, fibronectin and collagen type I in the normal pancreas was similar to that of quiescent PSCs and the expression profile in CP/PC tissues was similar to that of activated PSCs. Furthermore, galectin-1-overexpressing PSCs exhibited a significantly higher proliferation rate and migration ability, while galectin-1-silenced PSCs exhibited a significantly lower proliferation rate and migration ability than the control PSCs. The expression of fibronectin, collagen type I, α-SMA, MMP-2 and TIMP-1 was also significantly higher in the galectin-1-overexpressing PSCs than the control PSCs and this effect was found to be mediated by the TGF-β1/Smad pathway. The trends in the expression of these factors were reversed in the galectin-1-silenced PSCs. From these findings, it can be concluded that overexpression of galectin-1 promotes PSC activity (proliferation and migration) and stimulates fibrosis by increasing extracellular matrix synthesis and decreasing the MMP/TIMP ratio via the TGF-β1/Smad pathway. Thus, galectin-1 may be a novel candidate for reversing or halting fibrosis progression in CP/PC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Cell Proliferation
  • Female
  • Fibrosis / etiology*
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Follow-Up Studies
  • Galectin 1 / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Pancreatic Neoplasms / complications*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatic Stellate Cells / metabolism
  • Pancreatic Stellate Cells / pathology*
  • Pancreatitis, Chronic / complications*
  • Pancreatitis, Chronic / metabolism
  • Pancreatitis, Chronic / pathology
  • Prognosis
  • Smad2 Protein / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Galectin 1
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta1