Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage.
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.
Cardiovascular Translational Research. Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
Ernesto
E
Martinez-Martinez
Cardiovascular Translational Research. Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
Jaime
J
Ibarrola
INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Nancy, France.
Laurent
L
Calvier
Cardiovascular Translational Research. Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
Amaya
A
Fernandez-Celis
INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Nancy, France.
Celine
C
Leroy
Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Victoria
V
Cachofeiro
INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Nancy, France.
Patrick
P
Rossignol
Cardiovascular Translational Research. Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.|INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Nancy, France.
Natalia
N
Lopez-Andres
D058186:Acute Kidney Injury / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005355:Fibrosis; D037502:Galectin 3 / Q000037:antagonists & inhibitors* / Q000502:physiology; D007668:Kidney / Q000473:pathology*; D008297:Male; D009765:Obesity / Q000150:complications; D010368:Pectins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
D037502:Galectin 3; C586814:citrus pectin; D010368:Pectins