Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis

Am J Pathol. 2008 Feb;172(2):288-98. doi: 10.2353/ajpath.2008.070726. Epub 2008 Jan 17.


Macrophages have been proposed as a key cell type in the pathogenesis of renal fibrosis; however, the mechanism by which macrophages drive fibrosis is still unclear. We show that expression of galectin-3, a beta-galactoside-binding lectin, is up-regulated in a mouse model of progressive renal fibrosis (unilateral ureteric obstruction, UUO), and absence of galectin-3 protects against renal myofibroblast accumulation/activation and fibrosis. Furthermore, specific depletion of macrophages using CD11b-DTR mice reduces fibrosis severity after UUO demonstrating that macrophages are key cells in the pathogenesis of renal fibrosis. Disruption of the galectin-3 gene does not affect macrophage recruitment after UUO, or macrophage proinflammatory cytokine profiles in response to interferon-gamma/lipopolysaccharide. In addition, absence of galectin-3 does not affect transforming growth factor-beta expression or Smad 2/3 phosphorylation in obstructed kidneys. Adoptive transfer of wild-type but not galectin-3(-/-) macrophages did, however, restore the fibrotic phenotype in galectin-3(-/-) mice. Cross-over experiments using wild-type and galectin-3(-/-) macrophage supernatants and renal fibroblasts confirmed that secretion of galectin-3 by macrophages is critical in the activation of renal fibroblasts to a profibrotic phenotype. Therefore, we demonstrate for the first time that galectin-3 expression and secretion by macrophages is a major mechanism linking macrophages to the promotion of renal fibrosis.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Blotting, Western
  • Fibroblasts / metabolism
  • Fibrosis
  • Fluorescent Antibody Technique
  • Galectin 3 / metabolism*
  • Gene Expression
  • Immunohistochemistry
  • Kidney / immunology
  • Kidney / metabolism*
  • Kidney / pathology*
  • Macrophages / metabolism*
  • Mice
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ureteral Obstruction / complications


  • Galectin 3