Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β- and PDGF-like signals in hepatic stellate cells
| العنوان: | Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β- and PDGF-like signals in hepatic stellate cells |
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| المؤلفون: | Ming Heng Wu, Tsai Mu Cheng, Yuh Ling Chen, Chao Chiang Tu, Kuen Haur Lee, Szu Yuan Wu, Wan Lin Tsui, Che Chang Chang |
| المصدر: | Scientific Reports, Vol 7, Iss 1, Pp 1-16 (2017) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Liver Cirrhosis, Glycosylation, Galectin 1, medicine.medical_treatment, lcsh:Medicine, Article, Cell Line, 03 medical and health sciences, Mice, Cell Movement, Transforming Growth Factor beta, Neuropilin 1, Neuropilin, medicine, Hepatic Stellate Cells, Animals, Receptors, Platelet-Derived Growth Factor, lcsh:Science, Galectin, Mice, Knockout, Platelet-Derived Growth Factor, Multidisciplinary, biology, Chemistry, Growth factor, lcsh:R, Neuropilin-1, 3. Good health, Cell biology, 030104 developmental biology, biology.protein, Hepatic stellate cell, lcsh:Q, Signal transduction, Platelet-derived growth factor receptor, Transforming growth factor, Protein Binding, Signal Transduction |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::37999630a532b6f9a28b94129ee92b37Test http://link.springer.com/article/10.1038/s41598-017-11212-1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....37999630a532b6f9a28b94129ee92b37 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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