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PMID: 18202187 Published · ppublish English Journal Article

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

The American journal of pathology ·Vol. 172 ·No. 2 ·2008-02-00 ·Pages 288-98

Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C, Iredale JP, Liu FT, Hughes J, Sethi T

Abstract

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,metabolism,pathology Macrophages/metabolism Mice Reverse Transcriptase Polymerase Chain Reaction Ureteral Obstruction/complications
Chemicals
Galectin 3
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Henderson Neil C
The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Mackinnon Alison C
Farnworth Sarah L
Kipari Tiina
Haslett Christopher
Iredale John P
Liu Fu-Tong
Hughes Jeremy
Sethi Tariq
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.2353/ajpath.2008.070726
Published
2008-02-00
Epub
2008-00-17
Pages
288-98
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC2312353
Subset
IM
Grants
Medical Research Council · G0600033 · United Kingdom
External Links
PubMed source DOI: 10.2353/ajpath.2008.070726 PMC Full Text View journal details
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