Disease relevance of LGALS9

• Most importantly, recent data suggest a novel paradigm in which dysregulation of the TIM-3-galectin-9 pathway could underlie chronic autoimmune disease states, such as multiple sclerosis [1].
• None of the 13 patients with galectin-9-positive tumors and lymph node metastasis up to level II manifested distant metastasis [2].
• Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer [2].
• Association of galectin-9 expression in melanoma cells with prognosis of the patients bearing melanocytic tumors was further examined [3].
• Galectin-9 protein was strongly and homogeneously expressed in melanocytic nevi, but down-regulated in melanoma cells especially in metastatic lesions [3].

High impact information on LGALS9

• Tim-3 induces immunological tolerance, and engagement of the Tim-3 immunoglobulin variable (IgV) domain by galectin-9 is important for appropriate termination of T helper 1-immune responses [4].
• T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface [4].
• We provide data that galectin 9 is hUAT, the first identified human urate transporter. hUAT is a highly selective urate ion channel when inserted in lipid bilayers [5].
• Galectin-9 induces maturation of human monocyte-derived dendritic cells [6].
• A pan-caspase inhibitor (Z-VAD-FMK) inhibited Gal-9-induced apoptosis [7].

Chemical compound and disease context of LGALS9

• The surgically resected polyps and nasal turbinates were immunohistochemically stained using antibodies against EG2, human mast cell tryptase, CD3 and ecalectin [8].

Biological context of LGALS9

• Based on its deduced amino acid sequence, ecalectin is a 36-kDa protein consisting of 323 amino acids [9].
• In accordance with the nomenclature of known galectins, we suggest to designate this novel galactoside binding protein galectin-9 [10].
• Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins [2].
• Possible role of galectin-9 in cell aggregation and apoptosis of human melanoma cell lines and its clinical significance [3].
• 3. Stimulation of Tim-3 by its ligand galectin-9 results in increased phosphorylation of Y265, suggesting that this tyrosine residue plays an important role in downstream signalling events regulating T-cell fate [11].

Anatomical context of LGALS9

• IFN-gamma-induced production of galectin-9 by endothelial cells may play an important role in immune responses by regulating interactions between the vascular wall and eosinophils [12].
• Galectin-9 is a member of the galectin family and has been identified as an eosinophil chemoattractant produced by activated T lymphocytes [12].
• We have addressed the stimulation of galectin-9 expression in endothelial cells [12].
• The in situ endothelium from patients with inflammatory diseases was found to express galectin-9 [12].
• Galectin-9 (Gal-9) induced the apoptosis of not only T cell lines but also of other types of cell lines in a dose- and time-dependent manner [7].

Associations of LGALS9 with chemical compounds

• The apoptosis was suppressed by lactose, but not by sucrose, indicating that beta-galactoside binding is essential for Gal-9-induced apoptosis [7].
• A highly conserved tyrosine of Tim-3 is phosphorylated upon stimulation by its ligand galectin-9 [11].
• Human galectin 9, which is highly homologous to the rat urate transporter rUAT, has been reported to be a secreted or cytosolic protein [5].
• Regulation of galectin-9 by estradiol, progesterone, epidermal growth factor, and interferon-gamma in endometrial epithelial cells in vitro was studied [13].
• We found no significant effects of Simvastatin on the distribution of LMP1 and galectin 9 in NPC cell rafts [14].

Physical interactions of LGALS9

• Ecalectin did not mediate ECA activity by binding to the IL-5R or to CCR3 [15].

Regulatory relationships of LGALS9

• This adherence of eosinophils to HFL-1 cells was inhibited by both lactose and anti-galectin-9 Ab [16].

Other interactions of LGALS9

• Galectin-9 was detected in membrane and cytosolic fractions of human umbilical vein endothelial cells stimulated with interferon-gamma (IFN-gamma) [12].
• Interleukin-4, which induces eotaxin expression, did not affect the expression of galectin-9 [12].
• Regulatory mechanisms of galectin-9 and eotaxin-3 synthesis in epidermal keratinocytes: possible involvement of galectin-9 in dermal eosinophilia of Th1-polarized skin inflammation [17].
• On the one hand, IL-4, known as a Th2 cytokine, did not affect the galectin-9 expression in HFL-1 cells [16].
• Ecalectin is not related to any known cytokine or chemokine but rather is a variant of human galectin-9, a member of the large family of animal lectins that have affinity for beta-galactosides [9].

Analytical, diagnostic and therapeutic context of LGALS9

• Sequence analysis of the cDNA clone HOM-HD-21 revealed two homologous motifs known as lectin domains with galactoside binding capacity [10].
• RT-PCR, real-time PCR, and Western blot analyses revealed that both galectin-9 mRNA and protein in HFL-1 cells were up-regulated by IFN-gamma stimulation [16].
• The tumors of 84 patients with breast cancer were tested for galectin-9 expression by immunohistochemistry [2].
• The cumulative disease-free survival ratio for galectin-9-positive patients was more favorable than that for the galectin-9-negative group (P < 0.0001) [2].
• RT-PCR analysis revealed evident expression of galectin-9 mRNA in MM-BP but not in MM-RU [3].

References