Galectin-3

Galectin-3 is a is_associated_with::protein that in humans is encoded by the LGALS3 is_associated_with::gene. Galectin-3 is a member of the is_associated_with::lectin family, of which 14 is_associated_with::mammalian is_associated_with::galectins have been identified.

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

Galectin-3 is encoded by a single gene, LGALS3, located on chromosome 14, locus q21–q22. Galectin-3 is expressed in the nucleus, is_associated_with::cytoplasm, is_associated_with::mitochondrion, cell surface, and is_associated_with::extracellular space.

Function
Galectin-3 has an affinity for is_associated_with::beta-galactosides and exhibits is_associated_with::antimicrobial activity against bacteria and fungi.

This is_associated_with::protein has been shown to be involved in the following is_associated_with::biological processes: is_associated_with::cell adhesion, cell activation and chemoattraction, is_associated_with::cell growth and differentiation, is_associated_with::cell cycle, and is_associated_with::apoptosis. Given galectin-3’s broad biological functionality, it has been demonstrated to be involved in is_associated_with::cancer, is_associated_with::inflammation and is_associated_with::fibrosis, is_associated_with::heart disease, and is_associated_with::stroke. 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 is_associated_with::Ventricular remodeling.

Fibrosis
A correlation between galectin-3 expression levels and various types of is_associated_with::fibrosis has been found. Galectin-3 is upregulated in cases of liver fibrosis, renal fibrosis, and is_associated_with::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. Companies have developed galectin modulators that block the binding of galectins to carbohydrate structures. The galectin-3 inhibitor, TD139 has the potential to treat fibrosis.

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. In normal human, is_associated_with::murine, and rat cells galectin-3 levels are low. However as heart disease progresses, significant is_associated_with::upregulation of galectin-3 occurs in the is_associated_with::myocardium.

Galectin-3 also may be used as a is_associated_with::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. One study concluded that individuals with systolic heart failure of is_associated_with::ischaemic origin  and elevated galectin-3 levels may benefit from is_associated_with::statin treatment. Galectin-3 has also been associated as a factor promoting is_associated_with::ventricular remodeling following is_associated_with::mitral valve repair, and may identify patients requiring additional therapies to obtain beneficial is_associated_with::reverse remodeling.

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. is_associated_with::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 is_associated_with::therapeutic agents for cancer treatment.

is_associated_with::Overexpression and changes in sub- and inter-cellular localization of galectin-3 are commonly seen in is_associated_with::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 is_associated_with::cell growth and differentiation, chemoattraction, is_associated_with::apoptosis, is_associated_with::immunosuppression, is_associated_with::angiogenesis, adhesion, invasion and is_associated_with::metastasis.

Galectin-3 is_associated_with::overexpression promotes is_associated_with::neoplastic transformation and the maintenance of transformed is_associated_with::phenotypes as well as enhances the is_associated_with::tumour cell's adhesion to the is_associated_with::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 is_associated_with::tumour cell's evasion of the is_associated_with::immune system. Galectin-3 also helps promote is_associated_with::angiogenesis.

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

As a drug target to treat fibrosis
Galectin-3 is upregulated in patients with is_associated_with::idiopathic pulmonary fibrosis. The cells that receive galectin-3 stimulation (is_associated_with::fibroblasts, is_associated_with::epithelial cells, and is_associated_with::myofibroblasts) upregulated the formation of is_associated_with::fibrosis and collagen formation. 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 is_associated_with::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.

is_associated_with::Galecto Biotech is a research company focused on developing drugs using galectin-3 in treatment for is_associated_with::fibrosis, specifically is_associated_with::idiopathic pulmonary fibrosis. Galectin Therapeutics in the United States is also using is_associated_with::galectins for their research, finding recently that inhibition of galectin-3 significantly reduces is_associated_with::portal hypertension and is_associated_with::fibrosis in mice. is_associated_with::Chronic heart failure has been found to be indicated by a galectin-3 tests, using the ARCHITECT is_associated_with::immunochemistry platform developed by Abbott and BG Medicine, helping to determine which patients are most at risk for the disease. 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.

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. One approach to cancers with high galectin-3 expression is to use small molecule inhibition of galectin-3 to enhance treatment response.

Interactions
LGALS3 has been shown to interact with is_associated_with::LGALS3BP.

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