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Galectin-3 pharmacological inhibition attenuates early renal damage in spontaneously hypertensive rats.
- Source :
-
Journal of hypertension [J Hypertens] 2018 Feb; Vol. 36 (2), pp. 368-376. - Publication Year :
- 2018
-
Abstract
- Background: The pharmacological blockade of galectin-3 (Gal-3), a β-galactoside-binding lectin, reduces renal impairment in acute kidney injury, hyperaldosteronism or nephropathy. We herein investigated the effects of pharmacological Gal-3 inhibition by modified citrus pectin (MCP) in renal damage in spontaneously hypertensive rats (SHRs).<br />Methods and Results: Gal-3 inhibition did not modify blood pressure levels in 30-week-old SHR. Kidney weight was higher in SHR, with no effect of MCP treatment (100 mg/kg/day in the drinking water). Plasma creatinine and albuminuria were slightly but significantly increased in SHR and reduced by MCP, as well as plasma and urinary neutrophil gelatinase-associated lipocalin. In kidney from SHR, Gal-3 was upregulated, as well as the fibrotic markers (collagen type I, TGF-β and connective tissue growth factor) and tubulointerstitial fibrosis. MCP treatment reduced Gal-3 levels and fibrosis. The epithelial-mesenchymal transition (EMT) molecules (fibronectin, α-smooth muscle actin and β-catenin) were modified in SHR and normalized by Gal-3 inhibition. The inflammatory mediators (monocyte chemoattractant protein-1, osteopontin, cd68, cd80, cd44 and cd45) were elevated in SHR and attenuated by MCP. Renal damage markers (neutrophil gelatinase-associated lipocalin and kidney injury molecule-1) were augmented in SHR and improved by MCP. In renal epithelial normal rat kidney-52E cells, Gal-3 treatment induced EMT markers, whereas Gal-3 silencing attenuated EMT.<br />Conclusion: Gal-3 inhibition attenuated early renal damage in SHR as indicated by reduced albuminuria, improved renal function and decreased renal fibrosis, EMT and inflammation, independently of blood pressure levels. These data suggest that Gal-3 could be a potential therapeutic candidate for the prevention of early renal alterations in hypertension.
- Subjects :
- Actins metabolism
Acute Kidney Injury
Acute-Phase Proteins urine
Albuminuria drug therapy
Animals
Blood Pressure
Cell Line
Chemokine CCL2 metabolism
Collagen Type I metabolism
Connective Tissue Growth Factor metabolism
Creatinine blood
Epithelial-Mesenchymal Transition drug effects
Fibronectins metabolism
Fibrosis
Hypertension complications
Kidney Diseases etiology
Kidney Diseases pathology
Lipocalin-2
Lipocalins blood
Lipocalins urine
Male
Organ Size
Osteopontin metabolism
Proto-Oncogene Proteins blood
Proto-Oncogene Proteins urine
Rats
Rats, Inbred SHR
Transforming Growth Factor beta metabolism
Up-Regulation
beta Catenin metabolism
Antigens, CD metabolism
Galectin 3 antagonists & inhibitors
Hypertension drug therapy
Kidney pathology
Kidney Diseases prevention & control
Pectins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5598
- Volume :
- 36
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 28858976
- Full Text :
- https://doi.org/10.1097/HJH.0000000000001545