Galectin-3 modulates rat mesangial cell proliferation and matrix synthesisduring experimental glomerulonephritis induced by anti-Thy1.1 antibodies

Galectin-3 is a beta-galactoside-binding protein synthesized by macrophages and other inflammatory cells and expressed in various branching epithelia, including the developing kidney, The expression of galectin-3 has been stu died in a rat model of acute mesangial proliferative glomerulonephritis in which a single injection of anti-Thy1.1 antibodies leads to destruction of mesangial cells expressing a Thy1.1 epitope on their surface. The glomerula r lesion is characterized by expansion of the mesangial matrix, especially laminin and collagen type TV, and mesangial hypercellularity, Galectin-3 ex pression, which is sparse in mature rat kidney and confined to the apical f ace of some distal tubules, is increased within 1-3 days following antibody administration, with the recruitment of glomerular macrophages and pronoun ced neo-expression in the cytoplasm and at the basal face of distal tubules , At later times, galectin-3 is detected immunohistochemically in the repop ulating mesangial cell mass, preceding the extensive mesangial deposition o f laminin and collagen type IV. Mesangial cells in culture do not produce a ppreciable amounts of galectin-3 but do bind and endocytose exogenously add ed lectin, Addition of galectin-3 to primary cultures of mesangial cells pr epared from normal rats induces a 1.5-fold increase in the synthesis of col lagen type IV and it also acts in synergy with a quantitatively similar sti mulatory effect of transforming growth factor beta (TGF-beta) on matrix syn thesis. Exogenous galectin-3 prolongs the survival of mesangial cells in se rum-free cultures and also protects these cells against cytotoxic effects o f TGF-beta. The data support the notion that the increased expression and s ecretion of galectin-3 in infiltrating macrophages and in distal tubular ep ithelia, together with up-regulation of IL-1 beta and TGF-beta genes, play a role in mesangial hypercellularity in the progression of one model of inf lammatory renal disease. Copyright (C) 1999 John Wiley & Sons, Ltd.