Galectin-3 in Kidney Diseases: From an Old Protein to a New Therapeutic Target

Abstract

Galectin-3 (Gal-3) is a 30KDa lectin implicated in multiple pathophysiology pathways including renal damage and fibrosis. Gal-3 binds β-galactoside through its carbohydrate-recognition domain. From intra-cellular to extra-cellular localization, Gal-3 has multiple roles including transduction signal pathway, cell-to-cell adhesion, cell to extracellular matrix adhesion, and immunological chemoattractant protein. Moreover, Gal-3 has also been linked to kidney disease in both preclinical models and clinical studies. Gal-3 inhibition appears to improve renal disease in several pathological conditions, thus justifying the development of multiple drug inhibitors. This review aims to summarize the latest literature regarding Gal-3 in renal pathophysiology, from its role as a biomarker to its potential as a therapeutic agent.

Chronic intermittent hypoxia promotes glomerular hyperfiltration and potentiates hypoxia-evoked decreases in renal perfusion and PO2

“…KLF15, and E-Cadherin, which have fibrosis-suppressing activity and have been shown to be downregulated by ANG II and hypoxia ( Esteban et al, 2006 ; Lu et al, 2019 ), were decreased in cortical tissue from CIH relative to sham. Expression of pro-fibrotic CTGF, TIMP, Galectin 3, Snail, and VEGF (all of which are induced by hypoxia and/or ANG II ( Liu et al, 2017 ; Boutin et al, 2022 ; Khalaji et al, 2023 )), was significantly higher in cortical tissue from CIH vs sham, suggesting that CIH exposure promotes activation of pro-oxidative, pro-fibrotic signaling that may contribute to tissue damage and organ dysfunction.…”

Fecal and Urinary Adipokines as Disease Biomarkers

“…Given its involvement in multiple pathological settings, galectin-3 has become a therapeutic target, and genetic or pharmacological inhibition of galectin-3 improved renal dysfunction in different pathological conditions [ 171 ] and was also protective in experimental models of liver fibrosis [ 168 , 172 , 173 ].…”

“…Alternatively, the determination of plasma levels of fibrosis markers could be considered. However, they often lack specificity to provide information on organ-specific disease states [ 171 , 174 ]. Hence, the development of urine biomarkers to determine kidney fibrosis may be more appropriate for routine tests in the clinic or research-related and laboratory-based studies.…”

Biomarkers of Adverse Cardiovascular Events in Kidney Disease

“…Галектин-3 (Gal-3) -белок из семейства галектинов, b-галактозидсвязывающих лектинов, выполняющий важные функции во многих биологических процессах, включая сердечный и почечный фиброз и формирование СН [45]. Первоначально Gal-3 изучался как биомаркер повреждения сердца, но в нескольких последних исследованиях оценивалась его роль как биомаркера повреждения почек [46,47].…”