Renal fibrosis is a key feature of chronic kidney disease (CKD), driven by persistent inflammation, immune activation, and extracellular matrix accumulation. Galectin-3, a lectin involved in immune regulation and fibrosis, has been implicated in CKD progression, but its clinical and mechanistic roles remain incompletely defined. Galectin-3 expression was assessed in human CKD cohorts and correlated with renal function. Functional studies were performed in murine adenine-induced nephropathy and unilateral ureteral obstruction (UUO) models. Genetic deletion of Galectin-3 and pharmacological inhibition using GB1107 were used to evaluate its role in renal injury. Kidney fibrosis, inflammation, and function were analyzed by histology, serum biochemistry, RNA sequencing, and molecular assays. Galectin-3 was significantly upregulated in diseased human kidneys and correlated with renal dysfunction. In mouse models, Galectin-3 was induced in injured tubular epithelial cells. Galectin-3 deficiency significantly reduced renal fibrosis, with decreased serum creatinine, blood urea nitrogen, and α-SMA expression. Transcriptomic analysis showed suppression of NF-κB signaling–related genes in knockout kidneys. Pharmacological inhibition with GB1107 similarly reduced fibrosis and improved renal function. Galectin-3 promotes renal fibrosis by enhancing inflammatory and pro-fibrotic signaling. Targeting Galectin-3 genetically or pharmacologically may represent a therapeutic strategy to preserve renal function and further studies are required to determine whether targeting Galectin-3 can limit CKD progression in clinical settings.
Qin et al. (Mon,) studied this question.