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

Neil C. Henderson, Alison C. Mackinnon, Sarah Farnworth, Tiina Kipari, Christopher Haslett, John P. Iredale, Fu-Tong Liu, Jeremy Hughes, Tariq Sethi

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)288-298
Number of pages11
JournalThe American Journal of Pathology
Issue number2
Publication statusPublished - Feb 2008


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