Galectin-3 modulates rat mesangial cell proliferation and matrix synthesis during 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 studied 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 glomerular lesion is characterized by expansion of the mesangial matrix, especially laminin and collagen type IV, and mesangial hypercellularity. Galectin-3 expression, which is sparse in mature rat kidney and confined to the apical face of some distal tubules, is increased within 1-3 days following antibody administration, with the recruitment of glomerular macrophages and pronounced neo-expression in the cytoplasm and at the basal face of distal tubules. At later times, galectin-3 is detected immunohistochemically in the repopulating mesangial cell mass, preceding the extensive mesangial deposition of laminin and collagen type IV. Mesangial cells in culture do not produce appreciable amounts of galectin-3 but do bind and endocytose exogenously added lectin. Addition of galectin-3 to primary cultures of mesangial cells prepared from normal rats induces a 1.5-fold increase in the synthesis of collagen type IV and it also acts in synergy with a quantitatively similar stimulatory effect of transforming growth factor beta (TGF-beta) on matrix synthesis. Exogenous galectin-3 prolongs the survival of mesangial cells in serum-free cultures and also protects these cells against cytotoxic effects of TGF-beta. The data support the notion that the increased expression and secretion of galectin-3 in infiltrating macrophages and in distal tubular epithelia, together with up-regulation of IL-1beta and TGF-beta genes, play a role in mesangial hypercellularity in the progression of one model of inflammatory renal disease. Copyright 1999 John Wiley & Sons, Ltd.