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

Abstract

Galectin‐3 is a β‐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 β (TGF‐β) 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‐β. 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‐1β and TGF‐β genes, play a role in mesangial hypercellularity in the progression of one model of inflammatory renal disease. Copyright © 1999 John Wiley & Sons, Ltd.