2. Academic Validation
  3. Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β- and PDGF-like signals in hepatic stellate cells

Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β- and PDGF-like signals in hepatic stellate cells

  • Sci Rep. 2017 Sep 8;7(1):11006. doi: 10.1038/s41598-017-11212-1.
Ming-Heng Wu 1 2,  Yuh-Ling Chen 3,  Kuen-Haur Lee 4,  Che-Chang Chang 5,  Tsai-Mu Cheng 5,  Szu-Yuan Wu 6 7,  Chao-Chiang Tu 8,  Wan-Lin Tsui 5
Affiliations

Affiliations

  • 1 Graduate Institute of Translational Medicine, College of Medical Sciences and Technology, Taipei Medical University, Taipei, Taiwan. [email protected].
  • 2 Center for Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan. [email protected].
  • 3 Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 4 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Sciences and Technology, Taipei Medical University, Taipei, Taiwan.
  • 5 Graduate Institute of Translational Medicine, College of Medical Sciences and Technology, Taipei Medical University, Taipei, Taiwan.
  • 6 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
  • 7 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 8 Department of General Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
PMID: 28887481 DOI: 10.1038/s41598-017-11212-1
Abstract

Concomitant expressions of glycan-binding proteins and their bound glycans regulate many pathophysiologic processes, but this issue has not been addressed in liver fibrosis. Activation of hepatic stellate cells (HSCs) is a rate-limiting step in liver fibrosis and is an important target for liver fibrosis therapy. We previously reported that Galectin (Gal)-1, a β-galactoside-binding protein, regulates myofibroblast homeostasis in oral carcinoma and wound healing, but the role of Gal-1 in HSC migration and activation is unclear. Herein, we report that Gal-1 and its bound glycans were highly expressed in fibrotic livers and activated HSCs. The cell-surface glycome of activated HSCs facilitated Gal-1 binding, which upon recognition of the N-glycans on neuropilin (NRP)-1, activated platelet-derived growth factor (PDGF)- and transforming growth factor (TGF)-β-like signals to promote HSC migration and activation. In addition, blocking endogenous Gal-1 expression suppressed PDGF- and TGF-β1-induced signaling, migration, and gene expression in HSCs. Methionine and choline-deficient diet (MCD)-induced collagen deposition and HSC activation were attenuated in Gal-1-null mice compared to wild-type mice. In summary, we concluded that glycosylation-dependent Gal-1/NRP-1 interactions activate TGF-β and PDGF-like signaling to promote the migration and activation of HSCs. Therefore, targeting Gal-1/NRP-1 interactions could be developed into liver fibrosis therapy.

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