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.

中文翻译：

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糖基化依赖性半乳糖凝集素-1 /神经纤维蛋白-1相互作用通过激活肝星状细胞中的TGF-β-和PDGF-样信号促进肝纤维化。

聚糖结合蛋白及其结合的聚糖的伴随表达调节许多病理生理过程，但是在肝纤维化中尚未解决该问题。肝星状细胞（HSC）的激活是肝纤维化的限速步骤，并且是肝纤维化治疗的重要目标。我们先前曾报道过半乳糖凝集素（Gal）-1，一种β-半乳糖苷结合蛋白，在口腔癌和伤口愈合中调节肌纤维母细胞稳态，但尚不清楚Gal-1在HSC迁移和激活中的作用。在本文中，我们报道Gal-1及其结合的聚糖在纤维化肝脏和活化的HSC中高度表达。活化的HSC的细胞表面糖原促进了Gal-1结合，这在识别神经毛蛋白（NRP）-1上的N-聚糖后，激活血小板衍生生长因子（PDGF）和转化生长因子（TGF）-β样信号来促进HSC迁移和激活。另外，阻断内源性Gal-1表达抑制了HSC中PDGF-和TGF-β1诱导的信号传导，迁移和基因表达。与野生型小鼠相比，Gal-1-null小鼠的蛋氨酸和胆碱缺乏饮食（MCD）诱导的胶原沉积和HSC激活减弱。总之，我们得出的结论是，糖基化依赖性的Gal-1 / NRP-1相互作用激活TGF-β和PDGF样信号传导，从而促进HSC的迁移和激活。因此，靶向Gal-1 / NRP-1相互作用可以发展为肝纤维化治疗。HSC中的迁移和基因表达。与野生型小鼠相比，Gal-1-null小鼠的蛋氨酸和胆碱缺乏饮食（MCD）诱导的胶原蛋白沉积和HSC激活减弱。总之，我们得出的结论是，糖基化依赖性的Gal-1 / NRP-1相互作用激活TGF-β和PDGF样信号传导，从而促进HSC的迁移和激活。因此，靶向Gal-1 / NRP-1相互作用可以发展为肝纤维化治疗。HSC中的迁移和基因表达。与野生型小鼠相比，Gal-1-null小鼠的蛋氨酸和胆碱缺乏饮食（MCD）诱导的胶原蛋白沉积和HSC激活减弱。总之，我们得出的结论是，糖基化依赖性的Gal-1 / NRP-1相互作用激活TGF-β和PDGF样信号传导，从而促进HSC的迁移和激活。因此，靶向Gal-1 / NRP-1相互作用可以发展为肝纤维化治疗。