Galectin-3

Galectin-3 is a protein that in humans is encoded by the LGALS3 gene.[5][6] Galectin-3 is a member of the lectin family, of which 14 mammalian galectins have been identified.[7][8]

LGALS3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A3K, 1KJL, 1KJR, 2NMN, 2NMO, 2NN8, 2XG3, 3AYA, 3AYC, 3AYD, 3AYE, 3T1L, 3T1M, 3ZSJ, 3ZSK, 3ZSL, 3ZSM, 4BLI, 4BLJ, 4BM8, 4JC1, 4JCK, 4LBJ, 4LBK, 4LBL, 4LBM, 4LBN, 4LBO, 4R9A, 4R9B, 4R9C, 4R9D, 4RL7, 4XBN, 5H9R, 5H9P
Identifiers
Aliases	LGALS3, CBP35, GAL3, GALBP, GALIG, L31, LGALS2, MAC2, lectin, galactoside binding soluble 3, galectin 3
External IDs	OMIM: 153619 MGI: 96778 HomoloGene: 37608 GeneCards: LGALS3
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q22.3 Start 55,124,110 bp[1] End 55,145,423 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 C1 Start 47,367,751 bp[2] End 47,386,160 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • chemoattractant activity • IgE binding • laminin binding • carbohydrate binding • RNA binding • oligosaccharide binding • protein phosphatase inhibitor activity • protein phosphatase binding Cellular component • cytoplasm • membrane • extracellular matrix • cell membrane • immunological synapse • mitochondrial inner membrane • spliceosomal complex • extracellular exosome • cell nucleus • extracellular • secretory granule membrane • ficolin-1-rich granule membrane • galectin complex • extracellular region • cell surface • collagen-containing extracellular matrix Biological process • negative regulation of endocytosis • cell differentiation • regulation of T cell proliferation • negative regulation of immunological synapse formation • epithelial cell differentiation • monocyte chemotaxis • immune system process • mRNA processing • eosinophil chemotaxis • negative regulation of extrinsic apoptotic signaling pathway • positive regulation of mononuclear cell migration • neutrophil chemotaxis • negative regulation of T cell receptor signaling pathway • mononuclear cell migration • positive regulation of calcium ion import • macrophage chemotaxis • regulation of T cell apoptotic process • RNA splicing • positive regulation of dendritic cell differentiation • regulation of extrinsic apoptotic signaling pathway via death domain receptors • negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell • positive chemotaxis • innate immune system • neutrophil degranulation • antimicrobial humoral immune response mediated by antimicrobial peptide • regulation of myeloid cell differentiation • positive regulation of protein homodimerization activity • positive regulation of protein localization to plasma membrane • negative regulation of protein tyrosine phosphatase activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3958	16854
Ensembl	ENSG00000131981	ENSMUSG00000050335
UniProt	P17931	P16110
RefSeq (mRNA)	NM_001177388 NM_002306 NM_001357678	NM_001145953 NM_010705
RefSeq (protein)	NP_002297 NP_001344607	n/a
Location (UCSC)	Chr 14: 55.12 – 55.15 Mb	Chr 14: 47.37 – 47.39 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Galectin-3 is approximately 30 kDa and, like all galectins, contains a carbohydrate-recognition-binding domain (CRD) of about 130 amino acids that enable the specific binding of β-galactosides.[7][9][10][11]

Galectin-3 (Gal-3) is also a member of the beta-galactoside-binding protein family that plays an important role in cell-cell adhesion, cell-matrix interactions, macrophage activation, angiogenesis, metastasis, apoptosis.

Galectin-3 is encoded by a single gene, LGALS3, located on chromosome 14, locus q21–q22.[7][12] Galectin-3 is expressed in the nucleus, cytoplasm, mitochondrion, cell surface, and extracellular space.[7][9][10]

Function

Galectin-3 has an affinity for beta-galactosides and exhibits antimicrobial activity against bacteria and fungi.[8]

This protein has been shown to be involved in the following biological processes: cell adhesion, cell activation and chemoattraction, cell growth and differentiation, cell cycle, and apoptosis.[7] Given galectin-3's broad biological functionality, it has been demonstrated to be involved in cancer, inflammation and fibrosis, heart disease, and stroke.[7][11][13][14] Studies have also shown that the expression of galectin-3 is implicated in a variety of processes associated with heart failure, including myofibroblast proliferation, fibrogenesis, tissue repair, inflammation, and ventricular remodeling.[13][15][16]

Galectin-3 associates with the primary cilium and modulates renal cyst growth in congenital polycystic kidney disease.[17]

The functional roles of galectins in cellular response to membrane damage are rapidly expanding.[18][19][20] It has recently shown that Galectin-3 recruits ESCRTs to damaged lysosomes so that lysosomes can be repaired.[19]

Clinical significance

Fibrosis

A correlation between galectin-3 expression levels and various types of fibrosis has been found. Galectin-3 is upregulated in cases of liver fibrosis, renal fibrosis, and idiopathic pulmonary fibrosis (IPF). In several studies with mice deficient in or lacking galectin-3, conditions that caused control mice to develop IPF, renal, or liver fibrosis either induced limited fibrosis or failed to induce fibrosis entirely.[21][22][23] Companies have developed galectin modulators that block the binding of galectins to carbohydrate structures. The galectin-3 inhibitor, TD139 and GR-MD-02 have the potential to treat fibrosis.[23]

Cardiovascular disease

Elevated levels of galectin-3 have been found to be significantly associated with higher risk of death in both acute decompensated heart failure and chronic heart failure populations.[24][25] In normal human, murine, and rat cells galectin-3 levels are low. However, as heart disease progresses, significant upregulation of galectin-3 occurs in the myocardium.[26]

Galectin-3 also may be used as a biomarker to identify at risk individuals, and predict patient response to different drugs and therapies. For instance, galectin-3 levels could be used in early detection of failure-prone hearts and lead to intervention strategies including broad spectrum anti-inflammatory agents.[13] One study concluded that individuals with systolic heart failure of ischaemic origin and elevated galectin-3 levels may benefit from statin treatment.[27] Galectin-3 has also been associated as a factor promoting ventricular remodeling following mitral valve repair, and may identify patients requiring additional therapies to obtain beneficial reverse remodeling.[28]

Cancer

The wide variety of effects of galectin-3 on cancerous cells are due to the unique structure and various interaction properties of the molecule. Overexpression and changes in the localization of galectin-3 molecules affects the prognosis of the patient and targeting the actions of galectin-3 poses a promising therapeutic strategy for the development of effective therapeutic agents for cancer treatment.

Overexpression and changes in sub- and inter-cellular localization of galectin-3 are commonly seen in cancerous conditions. The many interaction and binding properties of galectin-3 influence various cell activities based on its location. Altered galectin-3 expression can affect cancer cell growth and differentiation, chemoattraction, apoptosis, immunosuppression, angiogenesis, adhesion, invasion and metastasis.[29]

Galectin-3 overexpression promotes neoplastic transformation and the maintenance of transformed phenotypes as well as enhances the tumour cell's adhesion to the extracellular matrix and increase metastatic spreading. Galectin-3 can be either an inhibitory or a promoting apoptotic depending on its sub-cellular localization. In immune regulation, galectin-3 can regulate immune cell activities and helps contribute to the tumour cell's evasion of the immune system. Galectin-3 also helps promote angiogenesis.[29]

The roles of galectins and galectin-3, in particular, in cancer have been heavily investigated.[30] Of note, galectin-3 has been suggested to play important roles in cancer metastasis.[31]

Clinical applications

As an indicator of Cardiovascular Risk

Chronic heart failure has been found to be indicated by a galectin-3 tests, using the ARCHITECT immunochemistry platform developed by BG Medicine and marketed by Abbott, helping to determine which patients are most at risk for the disease. This test is also offered on the VIDAS platform marketed by bioMérieux.[32] Pecta-Sol C binds to galectin-3 binding sites on the surfaces of cells as a preventative measure created by Isaac Eliaz in conjunction with EcoNugenics.[33]

Galectin-3 is upregulated in patients with idiopathic pulmonary fibrosis. The cells that receive galectin-3 stimulation (fibroblasts, epithelial cells, and myofibroblasts) upregulated the formation of fibrosis and collagen formation.[34] Fibrosis is necessary in many aspects of intrabody regeneration. The myocardial lining constantly undergoes necessary fibrosis, and the inhibition of galectin-3 interferes with myocardial fibrogenesis. A study concluded that drugs binding to galectin-3 will benefit those who have too much fibrosis on the heart, but it might potentially backfire for those who need heart restructuring.[34]

Galecto Biotech is another research company focused on developing drugs using galectin-3 in treatment for fibrosis, specifically idiopathic pulmonary fibrosis.[35] Galectin Therapeutics in the United States is also using galectins for their research, finding recently that inhibition of galectin-3 significantly reduces portal hypertension and fibrosis in mice.[36]

Biomarkers

Galectin-3 is increasingly being used as a diagnostic marker for different cancers. It can be screened for and used as a prognostic factor to predict the progression of the cancer. Galectin-3 has varying effects in different types of cancer.[37] One approach to cancers with high galectin-3 expression is to use small molecule inhibition of galectin-3 to enhance treatment response.[38]

Interactions

LGALS3 has been shown to interact with LGALS3BP.[39][40][41]

In melanocytic cells LGALS3 gene expression may be regulated by MITF.[42]

References

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.