Galactins bind specifically to β-galactoside through an evolutionarily conserved sequence element of the carbohydrate recognition domain (CRD). The unique member of the family is galectin-3. In addition to CRD, it also contains proline and a glycine-rich N-terminal domain (ND) through which oligomers can be formed.
Structural and Biochemical Characteristics
Galectin-3 is a secretory protein of ~30 kDa and belongs to a family of β-galactoside-binding animal lectins. In contrast to FcεRI and CD23, galectin-3 does not exist as a transmembrane protein. The structure of galectin-3 consists of a CRD linked to a non-lectin region of proline- and glycine-rich tandem repeats. Similar to all other galectin family members, galectin-3 lacks a classical signal for the secretory pathway. Galectin-3 resides in the cytosol or the nucleus, but has also been shown to associate with intracellular vesicles and has been found in exosomes from dendritic cells. Galectin-3 expression appears to be species-specific and differences between humans and mice are described. Similar to FcεRI, galectin-3 was found on humans but not murine eosinophils. Galectin-3 might thus be another IgE Fc-receptors for which species-specific expression patterns might hamper interpretation of murine studies.
Fig.1 Galectin family classification and structure of galectin-3. (Tan, 2021)
Galectin-3 as A Biomarker
Elevated serum levels of galectin-3 are found in many diseases including various types of autoimmune diseases and cancer. So far, the only FDA-approved application of galectin-3 as a biomarker is for the prognosis of chronic heart failure. However, galectin-3 has recently emerged also as a promising diagnostic marker for thyroid cancers.
Functions of The Soluble IgE Receptor Galectin-3 in The IgE Network
Galectin-3 is a versatile player of the immune system. Secreted galectin-3 can activate cells directly by binding to cell surface receptors. Alternatively, galectin-3 is endocytosed, permitting it to modify intracellular signaling pathways. A large number of intracellular as well as extracellular galectin-3 binding partners, therefore, allows this protein to play a role in a large variety of inflammatory responses. In the context of allergic reactions, it is important to note that extracellular galectin-3 is a potent activator of mast cells via crosslinking of IgE-loaded FcεRI or via crosslinking FcεRI directly in an IgE-independent manner. Galectin-3 was shown to induce inflammatory mediator release from IgE-sensitized as well as non-sensitized mast cells and human eosinophils.
Possible Role in Periodontal Diseases and Potential Therapeutic Target
By direct binding to microbes and modulation of their clearence, Galectin-3 can affect the composition of the microbial community in the oral cavity. Galectin-3 also modulates the function of many immune cells in the gingiva and gingival sulcus and thus can affect immune homeostasis. Therapeutic effects of Gal-3 inhibition in bacteria induced PBC and DSS induced colitis where intestinal microbiota contribute to disease pathogenesis indicate possible positive effects of Gal-3 inhibition in periodontitis. Recently, Gal-3 binding core-shell glyconanoparticles based on citrus pectin, with Gal-3 inhibition properties, have been designed for targeted and combination drug delivery.
Fig.2 Possible role of Gal-3 in the development of periodontal diseases by modulation of the key players in periodontitis pathogenesis. (Velickovic, 2021)
Galectin-3 Antagonists for Cancer Therapy
Tumor cells released galectin-3 was found to bind glycosylated receptors at the surface of tumor-infiltrating lymphocytes (TIL), forming glycoprotein-galectin lattices that could reduce the motility and functionality of TILs. Disruption of glycoprotein-galectin-3 lattices using anti-galectin-3 antibodies, or galectin-3 antagonists such as N-acetyllactosamine, GCS-100 (MCP-derived polysaccharide), or GM-CT-01 (a galactomannan from guar gum) boosted cytokine secretion by TIL. Moreover, the purified TFD compound also blocked T-cell apoptosis mediated by either recombinant, tumor-associated, or cancer patient serum-associated galectin-3.
Creative Biolabs has been dedicated to providing scientific and high-quality antibodies products and related services. Our products are tested for guaranteed potency by strict independent laboratory testing. Contact us to learn more.
References
- Tan, Y.; et al. Galectin-3: a key player in microglia-mediated neuroinflammation and Alzheimer's disease. Cell & Bioscience. 2021, 11(1): 1-13.
- Velickovic, M.; et al. Galectin-3, Possible Role in Pathogenesis of Periodontal Diseases and Potential Therapeutic Target. Frontiers in Pharmacology. 2021, 12.
KINDLY NOTE
!! For Research Use Only. Our products and services are NOT intended for diagnostic or therapeutic applications.
