Pharmacological inhibition of galectin-3 protects against hypertensive nephropathy

Frenay, Anne‐Roos S.; Yu, Lili; Velde, A. Rogier van der; Vreeswijk-Baudoin, Inge; López‐Andrés, Natalia; Goor, Harry van; Silljé, Herman H W; Ruifrok, W. P.; Boer, Rudolf A. de

doi:10.1152/ajprenal.00461.2014

Cited by 45 publications

(48 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with epidemiological data, functional galectin-3 manipulation has shown important proinflammatory and profibrotic effects of this lectin (26,83,84). On this basis, pharmacological galectin-3 inhibition with small-molecule competitive inhibitors, including GR-MD-02 (galactoarabino-rhamnogalaturonan), GM-CT-01 (galactomannan), and Nacetyllactosamine, prevents hypertensive nephropathy (86) and reverses diet-induced NASH and cirrhosis (87). GR-MD-02 was well tolerated and improved markers of hepatic fibrosis in a phase I RCT enrolling patients with NASH and advanced fibrosis (clinical trial reg.…”

Section: Targeting Molecular Effectors Of Inflammation and Fibrosismentioning

confidence: 54%

Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities

et al. 2016

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferatoractivated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium-glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium. EPIDEMIOLOGICAL EVIDENCE LINKING NAFLD AND CKDChronic kidney disease (CKD) affects up to 8% of the world's adult population, with its prevalence increasing in an aging population beset by lifestyle-associated diseases such as obesity, the metabolic syndrome, diabetes, hypertension, and smoking (1). CKD may progress to end-stage renal disease (ESRD) and is an important cardiovascular disease (CVD) risk factor. Importantly, most patients with CKD die as a result of CVD before renal replacement therapy is initiated (1).There is potential for improving recognition and treatment of CKD. In the Third National Health and Nutrition Survey, awareness among patients with stage 3 CKD was ,8% (1). Furthermore, ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and all-cause mortality remains unchanged in the CKD population (2). These data suggest that key pathogenetic mechanisms underlying

show abstract

Section: Targeting Molecular Effectors Of Inflammation and Fibrosismentioning

confidence: 54%

Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities

et al. 2016

View full text Add to dashboard Cite

show abstract

“…After administration of the galectin-3 inhibitor, a decrease in proteinuria, reduced renal damage and enhanced renal function were observed. In the control group of Sprague-Dawley rats, none of the considered parameters for hypertensive nephropathy changed after administering N-acetyllactosamine [83] . In a murine model of steatohepatitis, nonalcoholic steatohepatitis mice were treated with GR-MD-02, a drug that inhibits galectin-3.…”

Section: Experience With Galectin Inhibitorsmentioning

confidence: 92%

Galectin-3 in Renal Pathology: More Than Just an Innocent Bystander?

Desmedt

Delanghe

et al. 2016

Am J Nephrol

View full text Add to dashboard Cite

Background: Galectin-3 is a member of a closely related lectin family, which is detected in several vertebrate epithelial and myeloid cell types. This beta-galactoside-binding soluble protein plays an important role in multiple biological processes. Depending on its location, type of injury or site of damage, the effects by galectin-3 can be various and sometimes contrasting. Summary: In this review, we discuss the general characteristics and functions of galectin-3. More specifically, we focus on the role of galectin-3 in the onset and development of diabetic and non-diabetic nephropathies. Finally, the therapeutic potential of anti-galectin-3 inhibitors is discussed. Key Messages: Due to its multifunctional character, galectin-3 plays a pivotal role in interstitial fibrosis and progression of chronic kidney disease. Inhibition of galectin-3 may be a promising therapeutic strategy to prevent end-stage renal disease.

show abstract

“…Gal-3 is also involved in renal fibrosis, as shown by several animal studies [51,54], and plasma levels of Gal-3 are increased in several other diseases, including chronic obstructive pulmonary disease (COPD), and several types of cancer [55][56][57]. Therefore, it is likely that the observed increases in plasma levels of Gal-3 in HF are associated with increased cardiac Gal-3 production, but also with production in other organs and/or tissues.…”

Section: Fibrosis Marker Gal-3mentioning

confidence: 93%