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.
Highlights
Galectin-3 (Gal-3) is a lectin discovered in the early 80s in tumoral cells
Renal disease: -Phase I, open label study, evaluated the security of weekly doses of GCS-100 in patients with chronic kidney disease. (NCT01717248) -Phase IIa, placebo-controlled, randomized, single-blind study evaluated of weekly doses of GCS-100 in patients with chronic kidney disease and eGFR change. (NCT01843790) Cancer: -Phase II trials evaluated the reduction of metastasis and stabilized colorectal carcinomas during outcompeting Gal-3 in binding to its receptors. (NCT00110721)
In a long term follow up study of 1320 patients with type 2 diabetes and an eGFR ≥ 30 mL.min−1 1.73 m−2, Tan et al demonstrated that Gal-3 was independently associated with doubling of serum creatinine (HR 1.19 CI95%[1.14, 1.24], p < 0.001) even after adjusting for chronic renal risk factors, baseline eGFR, and albuminuria status [84]
Summary
The role of this protein has been studied in several organs and associated injuries [1–3] Whether it is cancer, cardiovascular, or renal diseases, its pathophysiology remains complex. The term “lectin” is derived from the Latin word “legere” which means “to collect” and defines a group of binding proteins that interact with multiple partners via a specific carbohydrate recognition domain (CRD) [4] Because of these interactions, lectins are implicated in a wide variety of pathways (e.g., from transduction pathway to cell-to-cell interaction) [5,6]. Gal-3 antagonist, soluble protein binding with CRD Unknown Kd. Renal disease: -Phase I, open label study, evaluated the security of weekly doses of GCS-100 in patients with chronic kidney disease. (NCT01717248) -Phase IIa, placebo-controlled, randomized, single-blind study evaluated of weekly doses of GCS-100 in patients with chronic kidney disease and eGFR change. Galecto inc (Ole Maaloes, Copenhagen, Denmark) GB1211: FDA approved from Galecto inc (Ole Maaloes, Copenhagen, Denmark)
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