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

Tang,Dong; Wu, Qi; Zhang,Jingqiu; Zhang,Hongpeng; Yuan,Zhongxu; Xu,Jiaming; Chong,Yang; Huang,Yuqin; Xiong,Qingquan; Wang,Sen; Tian,Ying; Lu,Yongdie; Ge,Xiao; Shen,Wenjing; Wang,Daorong

doi:10.3892/or.2018.6202

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

Authors:
- Dong Tang
- Qi Wu
- Jingqiu Zhang
- Hongpeng Zhang
- Zhongxu Yuan
- Jiaming Xu
- Yang Chong
- Yuqin Huang
- Qingquan Xiong
- Sen Wang
- Ying Tian
- Yongdie Lu
- Xiao Ge
- Wenjing Shen
- Daorong Wang
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Affiliations: Department of General Surgery, Institute of General Surgery, Northern Jiangsu Provincial People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Clinical Medicine, Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of General Surgery, Anhui Second Provincial People's Hospital, Hefei, Anhui 230000, P.R. China, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: January 9, 2018 https://doi.org/10.3892/or.2018.6202
Pages: 1347-1355

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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.

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