Journal
ONCOLOGY REPORTS
Volume 39, Issue 3, Pages 1347-1355Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2018.6202
Keywords
chronic pancreatitis; pancreatic cancer; pancreatic stellate cell; galectin-1; fibrosis
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Funding
- National Natural Science Funding of China [81572344]
- Postdoctoral Science Foundation of China [2013M530243]
- Science and Technology Development Funding of Yangzhou City [2012123]
- Jiangsu Province Natural Science Foundation of China [BK20140495]
- Six Big Talent Peak Projects of Jiangsu Province [2014-WSW-078]
- Postdoctoral Science Foundation of Jiangsu Province
- training project of key talents of youth medicine in Jiangsu Province [QNRC2016330]
- 'Promote Health Development by Science and Technology' program of Jiangsu Province [KF201225]
- academic science and technology innovation fund for college students [x20160750, x20160753, x20160774, x20160783]
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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, alpha-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, alpha-SMA, tissue inhibitors of metalloproteinases (TIMP)-1, MMP-2, Smad2 and TGF-beta 1. Furthermore, the effect of adding a TGF-beta 1 receptor inhibitor on the expression of these proteins was examined. The results revealed that the expression profile of desmin, beta-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, alpha-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-beta 1/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-beta 1/Smad pathway. Thus, galectin-1 may be a novel candidate for reversing or halting fibrosis progression in CP/PC.
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