Galectin-3 blockade reduces renal fibrosis in two normotensive experimental models of renal damage

Ernesto Martinez-Martinez, Jaime Ibarrola, Laurent Calvier, Amaya Fernandez-Celis, Celine Leroy, Victoria Cachofeiro, Patrick Rossignol, Natalia Lopez-Andres

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: Galectin-3 (Gal-3), a β-galactoside-binding lectin, is increased in kidney injury and its pharmacological blockade reduces renal damage in acute kidney injury, hyperaldosteronism or hypertensive nephropathy. We herein investigated the effects of pharmacological Gal-3 inhibition by modified citrus pectin (MCP) in early renal damage associated with obesity and aortic stenosis (AS). Results: Gal-3 was upregulated in kidneys from high fat diet (HFD) rats and in animals with partial occlusion of ascending aorta (AS). Urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL) and urinary albumin were enhanced in HFD and AS rats. In kidney from obese rats, fibrotic markers (collagen, TFG-β), epithelial-mesenchymal transition molecules (α-smooth muscle actin, E-cadherin), inflammatory mediator (osteopontin) and kidney injury marker (kidney injury molecule-1) were modified. In kidney from AS rats, fibrotic markers (collagen, CTGF), epithelial-mesenchymal transition molecules (fibronectin, α-smooth muscle actin, β-catenin, E-cadherin) and kidney injury markers (NGAL, kidney injury molecule-1) were altered. Histologic observations of obese and AS rat kidneys revealed tubulointerstitial fibrosis. The pharmacological inhibition of Gal-3 with MCP normalized renal Gal-3 levels as well as functional, histological and molecular alterations in obese and AS rats. Conclusions: In experimental models of mild kidney damage, the increase in renal Gal-3 expression paralleled with renal fibrosis, inflammation and damage, while these alterations were prevented by Gal-3 blockade. These data suggest that Gal-3 could be a new player in renal molecular, histological and functional alterations at early stages of kidney damage.

Original languageEnglish (US)
Article numbere0166272
JournalPloS one
Volume11
Issue number11
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

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Galectin 3
fibrosis
Fibrosis
Theoretical Models
kidneys
Kidney
Rats
Aortic Valve Stenosis
Lipocalins
Gelatinases
Molecules
Cadherins
Nutrition
Muscle
Actins
Collagen
Fats
rats
Wounds and Injuries
Galactosides

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Martinez-Martinez, E., Ibarrola, J., Calvier, L., Fernandez-Celis, A., Leroy, C., Cachofeiro, V., ... Lopez-Andres, N. (2016). Galectin-3 blockade reduces renal fibrosis in two normotensive experimental models of renal damage. PloS one, 11(11), [e0166272]. https://doi.org/10.1371/journal.pone.0166272

Galectin-3 blockade reduces renal fibrosis in two normotensive experimental models of renal damage. / Martinez-Martinez, Ernesto; Ibarrola, Jaime; Calvier, Laurent; Fernandez-Celis, Amaya; Leroy, Celine; Cachofeiro, Victoria; Rossignol, Patrick; Lopez-Andres, Natalia.

In: PloS one, Vol. 11, No. 11, e0166272, 01.11.2016.

Research output: Contribution to journalArticle

Martinez-Martinez, E, Ibarrola, J, Calvier, L, Fernandez-Celis, A, Leroy, C, Cachofeiro, V, Rossignol, P & Lopez-Andres, N 2016, 'Galectin-3 blockade reduces renal fibrosis in two normotensive experimental models of renal damage', PloS one, vol. 11, no. 11, e0166272. https://doi.org/10.1371/journal.pone.0166272
Martinez-Martinez E, Ibarrola J, Calvier L, Fernandez-Celis A, Leroy C, Cachofeiro V et al. Galectin-3 blockade reduces renal fibrosis in two normotensive experimental models of renal damage. PloS one. 2016 Nov 1;11(11). e0166272. https://doi.org/10.1371/journal.pone.0166272
Martinez-Martinez, Ernesto ; Ibarrola, Jaime ; Calvier, Laurent ; Fernandez-Celis, Amaya ; Leroy, Celine ; Cachofeiro, Victoria ; Rossignol, Patrick ; Lopez-Andres, Natalia. / Galectin-3 blockade reduces renal fibrosis in two normotensive experimental models of renal damage. In: PloS one. 2016 ; Vol. 11, No. 11.
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AU - Cachofeiro, Victoria

AU - Rossignol, Patrick

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N2 - Background: Galectin-3 (Gal-3), a β-galactoside-binding lectin, is increased in kidney injury and its pharmacological blockade reduces renal damage in acute kidney injury, hyperaldosteronism or hypertensive nephropathy. We herein investigated the effects of pharmacological Gal-3 inhibition by modified citrus pectin (MCP) in early renal damage associated with obesity and aortic stenosis (AS). Results: Gal-3 was upregulated in kidneys from high fat diet (HFD) rats and in animals with partial occlusion of ascending aorta (AS). Urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL) and urinary albumin were enhanced in HFD and AS rats. In kidney from obese rats, fibrotic markers (collagen, TFG-β), epithelial-mesenchymal transition molecules (α-smooth muscle actin, E-cadherin), inflammatory mediator (osteopontin) and kidney injury marker (kidney injury molecule-1) were modified. In kidney from AS rats, fibrotic markers (collagen, CTGF), epithelial-mesenchymal transition molecules (fibronectin, α-smooth muscle actin, β-catenin, E-cadherin) and kidney injury markers (NGAL, kidney injury molecule-1) were altered. Histologic observations of obese and AS rat kidneys revealed tubulointerstitial fibrosis. The pharmacological inhibition of Gal-3 with MCP normalized renal Gal-3 levels as well as functional, histological and molecular alterations in obese and AS rats. Conclusions: In experimental models of mild kidney damage, the increase in renal Gal-3 expression paralleled with renal fibrosis, inflammation and damage, while these alterations were prevented by Gal-3 blockade. These data suggest that Gal-3 could be a new player in renal molecular, histological and functional alterations at early stages of kidney damage.

AB - Background: Galectin-3 (Gal-3), a β-galactoside-binding lectin, is increased in kidney injury and its pharmacological blockade reduces renal damage in acute kidney injury, hyperaldosteronism or hypertensive nephropathy. We herein investigated the effects of pharmacological Gal-3 inhibition by modified citrus pectin (MCP) in early renal damage associated with obesity and aortic stenosis (AS). Results: Gal-3 was upregulated in kidneys from high fat diet (HFD) rats and in animals with partial occlusion of ascending aorta (AS). Urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL) and urinary albumin were enhanced in HFD and AS rats. In kidney from obese rats, fibrotic markers (collagen, TFG-β), epithelial-mesenchymal transition molecules (α-smooth muscle actin, E-cadherin), inflammatory mediator (osteopontin) and kidney injury marker (kidney injury molecule-1) were modified. In kidney from AS rats, fibrotic markers (collagen, CTGF), epithelial-mesenchymal transition molecules (fibronectin, α-smooth muscle actin, β-catenin, E-cadherin) and kidney injury markers (NGAL, kidney injury molecule-1) were altered. Histologic observations of obese and AS rat kidneys revealed tubulointerstitial fibrosis. The pharmacological inhibition of Gal-3 with MCP normalized renal Gal-3 levels as well as functional, histological and molecular alterations in obese and AS rats. Conclusions: In experimental models of mild kidney damage, the increase in renal Gal-3 expression paralleled with renal fibrosis, inflammation and damage, while these alterations were prevented by Gal-3 blockade. These data suggest that Gal-3 could be a new player in renal molecular, histological and functional alterations at early stages of kidney damage.

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