Galectins are a family of widely expressed β-galactoside-binding lectins in modulating “cell-to-cell” and “cell-to-matrix” interactions in all organisms ^[1][2][3][1,2,3]. Mammalian galectins have either one or two highly conserved carbohydrate recognition domains (CRDs), recognizing β-galactoside residues, to form complexes that crosslink glycosylated ligands ^[4][5][6][4,5,6].

Galectins have been classified into three subgroups according to their CRD number and function (Figure 1): (1) Proto-type galectins (galectin-1, -2, -5, -7, -10, -11, -13, -14, and -15), containing a single CRD that form non-covalent homodimers, (2) tandem-repeat galectins (galectin-4, -6, -8, -9, and -12), carrying two CRD motifs connected by a peptide linker, and (3) chimera-type galectin (galectin-3), which are characterized by having a single CRD and an amino-terminal polypeptide tail region ^[2][5][6][2,5,6]. All members of galectin family were numbered consecutively by order of discovery (Figure 1). Galectins are ubiquitously present in vertebrates, invertebrates, and also protists [1].

Galectins play important roles in cell-to-cell and cell-to-matrix interactions by binding to endogenous glycans. Galectin signaling can regulate cellular functions at the cell surface. Biological functions of galectins, which are not yet fully understood, include roles in development, tissue regeneration, regulation of immune cell activities, and other important cellular functions ^[1][2][1,2].

Galectins are important regulators of inflammatory responses and immune system. In fact, galectins are expressed in many inflammatory cells, such as macrophages [7]. Depending on the inflammatory environment, galectins promote pro-inflammatory or anti-inflammatory responses ^[2][5][6][2,5,6]. Recently, the galectin-mediated specific molecular recognition of glycans on the cell surface have revealed their roles as innate immune functions against potential pathogens and parasites. As a part of the innate immune system for microbial recognition/effector functions, galectins bind to exogenously exposed glycans on the surface of viruses, bacteria, fungi, and parasites [3].

2. Clinical Significance and Applications of Galectine-3 (Gal-3)

Gal-3, approximately 30 kDa chimera-type galectin, is expressed in the nucleus, cytoplasm, mitochondrion, cell surface, and extracellular space. Gal-3, to an equal or greater extent than other galectins, plays an important role in cell-to-cell or cell-to-matrix interactions, cell growth and differentiation, macrophage activation, antimicrobial activity, angiogenesis, and apoptosis [8]. Extracellular and intracellular activities of Gal-3 are shown in Figure 2, with references detailed in the caption. Recently, Gal-3 has been indicated to be involved in the following broad pathological processes: Inflammation [9], fibrosis, cell-to-cell ^[10][11][10,11] or cell-to-matrix [12] contacts, cell proliferation ^[13][14][13,14], and protection from apoptosis ^[15][16][15,16]. Furthermore, many studies have revealed that Gal-3 expression is detected in many disease conditions, such as heart disease ^{[17][18][19][20][21][22][23]}[17,18,19,20,21,22,23], kidney disease ^{[24][25][26][27]}[24,25,26,27], diabetes mellitus ^[24][25][28][24,25,28], viral infection ^{[29][30][31][32]}[29,30,31,32], autoimmune disease ^{[33][34][35][36]}[33,34,35,36], neurodegenerative disorders ^{[37][38][39][40][41][42]}[37,38,39,40,41,42], and tumor formation ^{[43][44][45][46][47][48][49][50][51][52]}[43,44,45,46,47,48,49,50,51,52]. Since Gal-3 is readily secreted to the cell surface and into biological fluids (e.g., serum and urine), from injured cells and inflammatory cells, Gal-3 may be used as a sensitive diagnostic or prognostic biomarker for various pathological conditions ^{[44][52][53][54]}[44,52,53,54]. Furthermore, Gal-3 may also be useful for detecting very early stage of some diseases. Gal-3 has already been used as a novel biomarker in the early detection of myocardial dysfunction and heart failure [55]. Gal-3 has been validated as a biomarker of fibrotic degeneration in acute myocarditis following cardiac viral infection. In an animal model of heart failure, serum Gal-3 levels was shown to be used as an diagnostic biomarker for early detection of cardiac degeneration in acute myocarditis [31] and acute myocardial infarction [56]. Furthermore, Gal-3 is also a good specific marker for indicating the early stage of glioma tumorigenesis [43]. Serum levels of Gal-3 are usually determined by enzyme-linked immunosorbent assay (ELISA) using commercially available materials ^[57][58][57,58]. The localization or time-course of Gal-3 expression in various organs are examined immunohistochemically using commercially available anti-Gal-3 antibodies [31]. Gal-3 levels may be changed by different clinical factors in patients, depending on the underlying pathological conditions. Some previous studies indicated contradicting results on the association between Gal-3 levels and the prediction of clinical outcomes ^[59][60][61][59,60,61]. These studies, however, might be limited by the insufficient size of the clinical sample. In this review, we discuss and summarize recent developments of the biomarker characteristics and long-term outcome prediction of Gal-3 in patients with various types of diseases (Table 1) as well as associated animal models (Table 2). Furthermore, we provide an overview of Gal-3 as a next-generation biomarker for detecting early stage of various diseases.