Tags

Type your tag names separated by a space and hit enter

Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage.
PLoS One 2016; 11(11):e0166272Plos

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.

Authors+Show Affiliations

Cardiovascular Translational Research. Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.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.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.Department of Physiology, School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, 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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27829066

Citation

Martinez-Martinez, Ernesto, et al. "Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage." PloS One, vol. 11, no. 11, 2016, pp. e0166272.
Martinez-Martinez E, Ibarrola J, Calvier L, et al. Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage. PLoS ONE. 2016;11(11):e0166272.
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), pp. e0166272. doi:10.1371/journal.pone.0166272.
Martinez-Martinez E, et al. Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage. PLoS ONE. 2016;11(11):e0166272. PubMed PMID: 27829066.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage. AU - Martinez-Martinez,Ernesto, AU - Ibarrola,Jaime, AU - Calvier,Laurent, AU - Fernandez-Celis,Amaya, AU - Leroy,Celine, AU - Cachofeiro,Victoria, AU - Rossignol,Patrick, AU - Lopez-Andres,Natalia, Y1 - 2016/11/09/ PY - 2016/09/13/received PY - 2016/10/25/accepted PY - 2016/11/10/entrez PY - 2016/11/10/pubmed PY - 2017/6/27/medline SP - e0166272 EP - e0166272 JF - PloS one JO - PLoS ONE VL - 11 IS - 11 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27829066/Galectin_3_Blockade_Reduces_Renal_Fibrosis_in_Two_Normotensive_Experimental_Models_of_Renal_Damage_ L2 - http://dx.plos.org/10.1371/journal.pone.0166272 DB - PRIME DP - Unbound Medicine ER -