title: Pharmacological inhibition of galectin-3 protects against hypertensive nephropathy.
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.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
authors.forename: Anne-Roos S
authors.initials: AR
authors.lastname: Frenay
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Radiation Therapy, Harbin Medical University Cancer Hospital, Harbin, China; and.
authors.forename: Lili
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
authors.forename: A Rogier
authors.initials: AR
authors.lastname: van der Velde
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
authors.forename: Inge
authors.initials: I
authors.lastname: Vreeswijk-Baudoin
authors.affiliation: Cardiovascular Translational Research, Navarra Biomed (Miguel Servet Foundation), Pamplona, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: López-Andrés
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
authors.forename: Herman H
authors.initials: HH
authors.lastname: Silljé
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
authors.forename: Willem P
authors.initials: WP
authors.lastname: Ruifrok
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; r.a.de.boer@umcg.nl.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
mesh_terms: D000606:Amino Sugars / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D037502:Galectin 3 / Q000037:antagonists & inhibitors*; D006973:Hypertension / Q000150:complications*; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D017207:Rats, Sprague-Dawley
chemical_list: D000606:Amino Sugars; D037502:Galectin 3; C000458:N-acetyllactosamine
keywords: TGR(mREN)27; chronic kidney disease; fibrosis; galectin-3; hypertension; renin-angiotensin system