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

Ming Heng Wu, Yuh Ling Chen, Kuen Haur Lee, Che Chang Chang, Tsai Mu Cheng, Szu Yuan Wu, Chao Chiang Tu, Wan Lin Tsui

研究成果: 雜誌貢獻文章

11 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號11006
期刊Scientific Reports
7
發行號1
DOIs
出版狀態已發佈 - 十二月 1 2017

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