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Pharmacological inhibition of galectin-3 protects against hypertensive nephropathy

Authors :
Harry van Goor
Inge Vreeswijk-Baudoin
Lili Yu
A. Rogier van der Velde
Anne-Roos S. Frenay
Willem P. T. Ruifrok
Rudolf A. de Boer
Natalia López-Andrés
Herman H W Silljé
Groningen Institute for Organ Transplantation (GIOT)
Groningen Kidney Center (GKC)
Cardiovascular Centre (CVC)
Source :
American journal of physiology-Renal physiology, 308(5), F500-F509. AMER PHYSIOLOGICAL SOC
Publication Year :
2015
Publisher :
American Physiological Society, 2015.

Abstract

Galectin-3 activation is involved in the pathogenesis of renal damage and fibrogenesis. Limited data are available to suggest that galectin-3-targeted intervention is a potential therapeutic candidate for the prevention of chronic kidney disease. Homozygous TGR(mREN)27 (REN2) rats develop severe high blood pressure (BP) and hypertensive end-organ damage, including nephropathy and heart failure. Male REN2 rats were treated with N-acetyllactosamine [galectin-3 inhibitor (Gal3i)] for 6 wk; untreated REN2 and Sprague-Dawley rats served as controls. We measured cardiac function with echocardiogram and invasive hemodynamics before termination. BP and proteinuria were measured at baseline and at 3 and 6 wk. Plasma creatinine was determined at 6 wk. Renal damage was assessed for focal glomerular sclerosis, glomerular desmin expression, glomerular and interstitial macrophages, kidney injury molecule-1 expression, and α-smooth muscle actin expression. Inflammatory cytokines and extracellular matrix proteinases were quantified by quantitative real-time PCR. Systolic BP was higher in control REN2 rats, with no effect of Gal3i treatment. Plasma creatinine and proteinuria were significantly increased in control REN2 rats; Gal3i treatment reduced both. Renal damage (focal glomerular sclerosis, desmin, interstitial macrophages, kidney injury molecule-1, α-smooth muscle actin, collagen type I, and collagen type III) was also improved by Gal3i. All inflammatory markers (CD68, IL-68, galectin-3, and monocyte chemoattractant protein-1) were elevated in control REN2 rats and attenuated by Gal3i. Markers of extracellular matrix turnover were marginally altered in untreated REN2 rats compared with Sprague-Dawley rats. In conclusion, galectin-3 inhibition attenuated hypertensive nephropathy, as indicated by reduced proteinuria, improved renal function, and decreased renal damage. Drugs binding to galectin-3 may be therapeutic candidates for the prevention of chronic kidney disease.

Details

ISSN :
15221466 and 1931857X
Volume :
308
Database :
OpenAIRE
Journal :
American Journal of Physiology-Renal Physiology
Accession number :
edsair.doi.dedup.....5dc4fac5727012cfd1717bc1fb3f1366
Full Text :
https://doi.org/10.1152/ajprenal.00461.2014