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. 2016 Nov 9;11(11):e0166272.
doi: 10.1371/journal.pone.0166272. eCollection 2016.

Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage

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Free PMC article

Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage

Ernesto Martinez-Martinez et al. PLoS One. .
Free PMC article

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Effects of pharmacological inhibition of Gal-3 on renal damage in obese rats.
Expression of mRNA of Gal-3 (A). Quantification of fibrotic markers expression (B). Representative microphotographs of renal sections stained with Sirius red (C). Quantification of tubulointerstitial fibrosis (D). Expression of epithelial-mesenchymal transition molecules (E). Expression of inflammatory mediators (F). Expression of kidney damage markers (G). Magnification of the microphotographs 40x. Histogram bars represent the mean ± SEM of each group of animals (n ≥ 7 per group) in arbitrary units or as a percentage of staining normalized to HPRT and β-actin for cDNA. *p<0.05 vs. control group; $p<0.05 vs HFD group.
Fig 2
Fig 2. Effects of pharmacological inhibition of Gal-3 on renal damage in AS rats.
Expression of Gal-3 (A). Quantification of fibrotic markers expression (B). Representative microphotographs of renal sections stained with Sirius red (C). Quantification of tubulointerstitial fibrosis (D). Expression of epithelial-mesenchymal transition molecules (E). Expression of inflammatory mediators (F). Expression of kidney damage markers (G). Magnification of the microphotographs 40x. Histogram bars represent the mean ± SEM of each group of animals (n ≥ 7 per group) in arbitrary units or as a percentage of staining normalized to HPRT and β-actin for cDNA. *p<0.05 vs. control group; $p<0.05 vs AS group.

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Grant support

This work was supported by Miguel Servet contract CP13/00221 from the “Instituto de Salud Carlos III-FEDER”, Fondo de Investigaciones Sanitarias [PI15/02160] “One way to make Europe”, FIBROTARGETS project (Grant agreement number FP7 #602904), Red de Investigación Cardiovascular del ISCIII (RIC; RD12/0042/0033), Plan Estatal I+D+I 2013-2016. PR was supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” programme (reference: ANR-15-RHUS-0004).
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