| 2020 |
Exosomal LGALS9 derived from glioblastoma cells binds to the TIM-3 receptor on dendritic cells in the cerebrospinal fluid, inhibiting antigen recognition, processing, and presentation by DCs, thereby preventing cytotoxic T-cell-mediated antitumor immune responses. Blocking exosomal LGALS9 secretion restored DC antigen-presenting activity and induced durable antitumor immunity in mice. |
Proteomics of CSF exosomes, receptor-ligand binding assay (TIM-3/LGALS9), in vivo mouse model with LGALS9 secretion blockade, functional DC and T-cell assays |
Cell death & disease |
Medium |
33093453
|
| 2015 |
Recombinant LGALS9 (rLGALS9) internalizes via early and late endosomes and accumulates in the lysosomal compartment of KRAS-mutant colorectal cancer cells, where it acts as a lysosomal inhibitor blocking autophagosome-lysosome fusion. This leads to autophagosome accumulation, excessive lysosomal swelling, and cell death selectively in KRAS-mutant (but not BRAF-mutant) CRC cells with elevated basal autophagic flux. |
Live cell imaging (endosomal/lysosomal tracking), autophagy flux assays, cell viability assays, genetic mutant cell lines (KRAS vs BRAF) |
Autophagy |
Medium |
26086204
|
| 2013 |
Endothelial cells express five LGALS9 splice variants (including two novel ones) confined to exons 5, 6, and 10. Transfection of HMEC with the galectin-9Δ5 splice variant increased proliferation; exogenous recombinant galectin-9Δ5 protein dose-dependently reduced endothelial cell proliferation and migration in vitro and induced a small inhibitory effect on angiogenesis in vivo, while also enhancing sprouting toward a galectin-9Δ5 gradient. |
Transfection/overexpression in HMEC, recombinant protein treatment, in vitro proliferation and migration assays, in vivo angiogenesis assay |
Biochimica et biophysica acta |
Medium |
24333696
|
| 2013 |
The LGALS9 D5 isoform suppresses interferon-gamma production by decidual natural killer cells. Decidual LGALS9 expression is deregulated in a mouse model of spontaneous abortion, and decreased LGALS9 D5/10 isoform expression is associated with spontaneous abortion in humans. |
Real-time PCR, immunohistochemistry, functional NK cell cytokine assay (IFN-γ production), mouse model of spontaneous abortion |
Biology of reproduction |
Medium |
23242525
|
| 2021 |
Galectin-9 (Gal-9/LGALS9) binds to peroxiredoxin-2 (PRDX2) in a sugar chain-independent manner. In 3T3-L1 adipocytes, Gal-9 knockdown shifts PRDX2 from its oxidized dimer form to the reduced monomer form under oxidative stress. Lgals9-deficient mice are resistant to diet-induced obesity with reduced adipose tissue and improved glucose tolerance, and bone marrow transplant experiments indicate the effect is non-hematopoietic-cell-autonomous. |
nanoLC-MS/MS, co-immunoprecipitation, pull-down assay, Gal-9 knockdown in adipocytes, western blot (PRDX2 redox state), Lgals9 knockout mouse with bone marrow transplantation |
Scientific reports |
Medium |
33727589
|
| 2018 |
Lgals9 deficiency in BALB/c mice protected against pristane-induced lupus nephritis, arthritis, and lipogranuloma formation without altering T-cell or B-cell subset composition in spleen or peritoneum, and without affecting the TLR7–type I interferon pathway. The protective effect was mediated through targeting of activated macrophages. |
Lgals9 knockout mouse model (pristane-induced lupus), histopathology, flow cytometry of immune subsets, cytokine profiling from peritoneal macrophages |
Arthritis & rheumatology |
Medium |
29481735
|
| 2021 |
LGALS9 transcription in endometrial stromal cells is upregulated by HAND2 and downregulated by FOXO1. Phosphorylated FOXO1 (pFOXO1) cannot bind DNA and thus cannot directly suppress LGALS9 transcription, so the phosphorylation status of FOXO1 and expression of HAND2 together determine LGALS9 mRNA levels during decidualization. |
Promoter-reporter transcriptional activity assays, siRNA knockdown of HAND2 and FOXO1, RT-qPCR, phospho-FOXO1 chromatin binding assay |
Molecular human reproduction |
Medium |
34581822
|
| 2020 |
Histone H3K9 and H3K14 acetylation at the LGALS9 promoter correlates with LGALS9 mRNA levels in cervical cancer cells, while CpG methylation at the promoter does not show hypermethylation associated with low LGALS9 expression. This suggests histone acetylation, not DNA methylation, is the primary epigenetic regulator of LGALS9 transcription. |
Chromatin immunoprecipitation (ChIP) for H3K9ac and H3K14ac, bisulfite sequencing for CpG methylation, RT-qPCR |
FEBS open bio |
Low |
32902187
|
| 2025 |
In early-stage endometrial cancer, CD47⁺ epithelial cells interact with macrophages through the CD47–HCK (Hemopoietic Cell Kinase) axis, driving macrophage secretion of LGALS9, IL-10, and TGF-β1. Macrophage-derived LGALS9 in turn reinforces EC cell proliferation via CD47, establishing a positive feedback loop (CD47–HCK–LGALS9). ERRγ was identified as an upstream transcriptional regulator of CD47, suppressible by progesterone. |
GST pull-down mass spectrometry, molecular docking, CUT&Tag (transcription factor identification), organoid–macrophage co-culture model, flow cytometry, CCK-8 proliferation assay |
Molecular cancer |
Medium |
41437376
|
| 2025 |
Rhamnose binds to sites V39, D40, and T101 of CEACAM1, promoting the interaction between CEACAM1 and LGALS9, which increases DUSP1 protein levels, inhibits p38 phosphorylation, and thereby attenuates LPS-triggered proinflammatory cytokine expression in macrophages. |
In vitro macrophage binding assays, Co-immunoprecipitation (CEACAM1–LGALS9), western blot (DUSP1, p-p38), LPS-induced endotoxic mouse model, site-directed mutagenesis/docking for binding sites |
Acta biochimica et biophysica Sinica |
Medium |
40708539
|
| 2025 |
Recombinant Lgals9 (rLgals9) treatment polarized macrophages toward the M2b phenotype at appropriate concentrations in vitro, as validated by flow cytometry and ELISA. Single-cell RNA sequencing showed significant downregulation of Lgals9 in macrophages after mouse heart transplantation. |
Recombinant protein treatment of macrophages, flow cytometry (M2b polarization markers), ELISA, scRNA-seq, RT-qPCR, western blot |
Journal of leukocyte biology |
Low |
39835675
|
| 2025 |
In gastric cancer, myeloid cell-derived LGALS9 binds to P4HB (beta-subunit of prolyl 4-hydroxylase) on epithelial cells as a ligand-receptor pair. Activation of P4HB by LGALS9 enhanced proliferation, epithelial-mesenchymal transition (EMT), and lipid metabolism in gastric cancer cells; pharmacological inhibition of P4HB reversed these effects. |
Single-cell RNA sequencing (ligand-receptor inference), functional experiments with LGALS9 treatment and P4HB inhibition, proliferation assays, EMT marker analysis |
Journal of cellular and molecular medicine |
Low |
40534096
|
| 2026 |
LGALS9 blockade (via adenoviral immunization) enhanced dendritic cell activation and maturation (upregulating CD80, CD86, MHC-II, CD40), promoted CD8+ T-cell priming and expansion, and disrupted the LGALS9/TIM-3 inhibitory axis via neutralizing antibodies, alleviating T-cell exhaustion in prostate cancer models. |
Adenoviral vector immunization, flow cytometry, ELISA, ELISpot, cytotoxic T lymphocyte assay, cell depletion experiments, in vivo mouse tumor models |
Journal for immunotherapy of cancer |
Medium |
42103355
|
| 2024 |
In osteoarthritis, LGALS9 exacerbates inflammatory responses by activating JNK and ERK1/2 (MAPK) signaling pathways. RNAi-mediated knockdown and lentiviral overexpression/knockdown in in vitro and in vivo OA models confirmed this regulatory role. |
RNAi knockdown, lentiviral overexpression/knockdown, western blot, qRT-PCR, immunofluorescence, safranin fast green staining, in vivo OA model |
International journal of biological macromolecules |
Medium |
39278441
|