title: Role of galectin-3 in diabetic nephropathy.
abstract: The advanced glycosylation end products (AGE) participate in the pathogenesis of nephropathy and other diabetic complications through several mechanisms, including their binding to cell surface receptors. The AGE receptors include RAGE, the macrophage scavenger receptors, OST-48 (AGE-R1), 80K-H (AGE-R2), and galectin-3 (AGE-R3). Galectin-3 interacts with the beta-galactoside residues of cell surface and matrix glycoproteins via the carbohydrate recognition domain and with intracellular proteins via peptide-peptide associations mediated by its N-terminus domain. These structural properties enable galectin-3 to exert multiple functions, including the mRNA splicing activity, the control of cell cycle, the regulation of cell adhesion, the modulation of allergic reactions, and the binding of AGE. The lack of transmembrane anchor sequence or signal peptide suggests that it is associated with other AGE receptors, possibly AGE-R1 and AGE-R2, to form an AGE-receptor complex, rather than playing an independent role. In target tissues of diabetic vascular complications, such as the endothelium and mesangium, galectin-3 is weakly expressed under basal conditions and is markedly upregulated by the diabetic milieu (and to a lesser extent by aging). Galectin-3-deficient mice were found to develop accelerated diabetic glomerulopathy versus the wild-type animals, as evidenced by the more pronounced increase in proteinuria, mesangial expansion, and matrix gene expression. This was associated with a more marked renal/glomerular AGE accumulation, suggesting that it was attributable to the lack of galectin-3 AGE-receptor function. These data indicate that galectin-3 is upregulated under diabetic conditions and is operating in vivo to provide protection toward AGE-induced tissue injury, as opposed to RAGE.
authors.affiliation: Laboratory of Metabolism and Pathological Biochemistry, Section of Endocrine Biochemistry, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Iacobini
authors.forename: Lorena
authors.initials: L
authors.lastname: Amadio
authors.forename: Giovanna
authors.initials: G
authors.lastname: Oddi
authors.forename: Carlo
authors.initials: C
authors.lastname: Ricci
authors.forename: Paola
authors.initials: P
authors.lastname: Barsotti
authors.forename: Serena
authors.initials: S
authors.lastname: Missori
authors.forename: Mariella
authors.initials: M
authors.lastname: Sorcini
authors.forename: Umberto
authors.initials: U
authors.lastname: Di Mario
authors.forename: Flavia
authors.initials: F
authors.lastname: Pricci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pugliese
mesh_terms: D000818:Animals; D019610:Cytoprotection; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology*; D037502:Galectin 3 / Q000737:chemistry / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D037502:Galectin 3; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic