Content area
Full text
1. Introduction
Galectins are a family of β-galactoside-binding lectins with ≥1 evolutionary conserved carbohydrate-recognition domain (CRD) (1). At present, 15 galectins have been identified in mammals, and are divided into three types based on domain organization as follows: i) Prototype galectins with one single CRD; ii) tandem-repeat galectins with two CRDs; iii) chimera-type galectins with a single CRD connected to a long, flexible N-terminal domain (1–3). Note that Galectin-3 is the only chimera-type galectin. Human galectin-3 is a 35-kDa protein that is coded by a single gene, LGALS3, located on chromosome 14. The N-terminal domain of galectin-3 is essential for its multimerization, sensitive to proteolysis by matrix metalloproteinases and may participate in the interaction with other intracellular proteins (3). Furthermore, the first 12 amino acids of galectin-3 are necessary for its secretion and nuclear translocation (4,5). The C-terminal CRD of galectin is responsible for its interaction with glycoconjugates containing N-acetyllactosamine. Thus, galectin-3 binds proteins in a carbohydrate-dependent and -independent manner.
Galectin-3 is widely expressed in human tissues, including all types of immune cell (macrophages, monocytes, dendritic cells, eosinophils, mast cells, natural killer cells, and activated T and B cells), epithelial cells, endothelial cells and sensory neurons (3,6). The expression of galectin-3 in tissues is developmentally regulated; it is more abundant during embryogenesis and development compared with adult life (7). Furthermore, during the early stages of embryogenesis, its expression pattern is more specific, located predominantly in the epithelia, kidney, chondrocytes and liver (8). However, galectin-3-knockout mice are viable without obvious abnormalities with the exception of premature senescence (9,10).
Galectin-3 is predominantly located in the cytoplasm and shuttles into the nucleus (Fig. 1). In addition, it is secreted to the cell surface and into biological fluids (3). The different locations of galectin-3 contribute to its various functions. In the cytoplasm, galectin-3 is important for cell survival, due to its interaction with certain survival-associated proteins, including B-cell lymphoma-2 (Bcl-2) and activated guanosine-5′-triphosphate (GTP)-bound K-Ras. In the nucleus, galectin-3 promotes pre-mRNA splicing and regulates gene transcription, whereas extracellular galectin-3 modulates cell-cell interactions, including between epithelial cells and the extracellular matrix. Thus, it is involved in cell differentiation, inflammation, fibrogenesis and the host defense (3,11). Therefore, galectin-3 is pivotal in numerous biological activities including cell growth, apoptosis, pre-mRNA splicing, differentiation,...