Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells

Hsieh, Sheng-Hung; Ying, Nien Wen; Wu, Meng Hsing; Chiang, Wei Fan; Hsu, Chien-Lung; Wong, Tai‐Chee; Jin, Ying; Hong, Tse-Ming; Chen, Y. L.

doi:10.1038/sj.onc.1211029

Cited by 191 publications

(206 citation statements)

References 29 publications

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“…44 Gal-1 was previously described as an endogenous ligand for NRP-1 expressed in vascular cells, where it stimulates endothelial cell signaling and function. 45 Specific carbohydrate-dependent interactions between Gal-1 and NRP-1 have been demonstrated in cell-free systems using surface plasmon resonance analysis. 45 In our experiments, Gal-1 but not M-Gal-1 or Gal-1 (N46D) lacking carbohydrate-binding activity showed robust capacity to regenerate axons via blockade of Sema3A binding, suggesting that the neuroregenerative effects of this lectin are highly dependent on dimerization and cross-linking of cell surface glycans on NRP-1.…”

Section: Discussionmentioning

confidence: 99%

“…45 Specific carbohydrate-dependent interactions between Gal-1 and NRP-1 have been demonstrated in cell-free systems using surface plasmon resonance analysis. 45 In our experiments, Gal-1 but not M-Gal-1 or Gal-1 (N46D) lacking carbohydrate-binding activity showed robust capacity to regenerate axons via blockade of Sema3A binding, suggesting that the neuroregenerative effects of this lectin are highly dependent on dimerization and cross-linking of cell surface glycans on NRP-1. This hypothesis was supported by immunoprecipitation experiments showing that only WT Gal-1, but not M-Gal-1, binds to the NRP-1/PlexinA4 complex and blocks the Sema3A pathway.…”

Section: Discussionmentioning

confidence: 99%

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Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

et al. 2014

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Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor complex. Here, we show that galectin-1 (Gal-1), an endogenous glycan-binding protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. Although both Gal-1 and its monomeric variant contribute to de-activation of microglia, only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this lectin for the treatment of SCI patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

et al. 2014

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“…40 Rat galectin-3 cDNA fragment (B900 bp) with the stop codon TAA mutated to CAA was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of mRNA from rat spleen with sense primer 5 0 -AACGGATCCAATGGCAGACGG-3 0 and antisense primer 5 0 -CTTACCGGTTG GATCATGGCGTG-3 0 , in which a BamHI site and an AgeI site were introduced onto the 5 0 -end and the 3 0 -end, respectively. The resulting PCR product was digested with BamHI and AgeI, and fused inframe and upstream to the coding region of GFP in pEGFP-N1 (Clontech, Palo Alto, CA, USA) at the BamHI/AgeI sites, yielding pEGFP-N1/Gal3.…”

Section: Construction Of Plasmidsmentioning

confidence: 99%

“…After 3 days, cell lysates were examined for the expression of galectin-3 by immunoblotting. Antibodies against human galectin-1 obtained from rabbit immune serum, 40 rat galectin-3 (Santa Cruz, Santa Cruz, CA, USA), GFP (Santa Cruz) and b-actin (Sigma-Aldrich, St Louis, MO, USA) were used. Signals were detected by chemiluminescence, and intensity was quantitated by densitometry in some blots.…”

Section: Immunoblot Histological and Immunohistochemical Analysesmentioning

confidence: 99%

Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis

et al. 2010

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Different members of the galectin family may have inhibitory or stimulatory roles in controlling immune responses and regulating inflammatory reactions in autoimmune diseases such as rheumatoid arthritis (RA). A hypothetical model of a cross talk between galectin-1 and galectin-3 has been established in the circumstance of rheumatoid joints. As galectin-3 is a positive regulator and galectin-1 is a negative regulator of inflammation and autoimmune responses, in this study we evaluated the effects of local knockdown of galectin-3 or overexpression of galectin-1 on ameliorating collagen-induced arthritis (CIA) in rats. Lentiviral vectors encoding galectin-3 small hairpin RNA (shRNA) and galectin-1, as well as two control vectors expressing luciferase shRNA and green fluorescent protein, were individually injected intra-articularly into the ankle joints of rats with CIA, and their treatment responses were monitored by measuring the clinical, radiological and histological changes. Our results show that both knockdown of galectin-3 and overexpression of galectin-1 induced higher percentages of antigen-induced T-cell death in the lymph node cells from arthritic rats. Furthermore, these treatments significantly reduced articular index scores, radiographic scores and histological scores, accompanied with decreased T-cell infiltrates and reduced microvessel density in the ankle joints. Our findings implicate galectin-3 and galectin-1 as potential therapeutic targets for the treatment of RA.

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“…Oxidized Gal1 has been suggested to bind to macrophages and stimulate them to release some factor which promotes axon outgrowth and Schwann cell migration [11,12]. However, recent studies have also identified Gal1 as a novel ligand of neuropilin-1 [34]. Neuropilin-1 acts as a receptor for both class 3 semaphorins and vascular endothelial growth factor [35], two factors of known importance for motor neuron guidance and survival [36,37].…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 expression in innervated and denervated skeletal muscle

Svensson¹,

Tågerud²

2009

Cellular and Molecular Biology Letters

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Galectin-1 is a soluble carbohydrate-binding protein with a particularly high expression in skeletal muscle. Galectin-1 has been implicated in skeletal muscle development and in adult muscle regeneration, but also in the degeneration of neuronal processes and/or in peripheral nerve regeneration. Exogenously supplied oxidized galectin-1, which lacks carbohydrate-binding properties, has been shown to promote neurite outgrowth after sciatic nerve sectioning. In this study, we compared the expression of galectin-1 mRNA and immunoreactivity in innervated and denervated mouse and rat hind-limb and hemidiaphragm muscles. The results show that galectin-1 mRNA expression and immunoreactivity are up-regulated following denervation. The galectin-1 mRNA is expressed in the extrasynaptic and perisynaptic regions of the muscle, and its immunoreactivity can be detected in both regions by Western blot analysis. The results are compatible with a role for galectin-1 in facilitating reinnervation of denervated skeletal muscle.

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Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells

Cited by 191 publications

References 29 publications

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis

Galectin-1 expression in innervated and denervated skeletal muscle

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