| First Author | Wu MH | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 11006 |
| PubMed ID | 28887481 | Mgi Jnum | J:256555 |
| Mgi Id | MGI:6109585 | Doi | 10.1038/s41598-017-11212-1 |
| Citation | Wu MH, et al. (2017) Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-beta- and PDGF-like signals in hepatic stellate cells. Sci Rep 7(1):11006 |
| abstractText | 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 beta-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)-beta-like signals to promote HSC migration and activation. In addition, blocking endogenous Gal-1 expression suppressed PDGF- and TGF-beta1-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-beta 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. |
