Targeting Galectin-3 Mitigates Chronic Kidney Fibrosis and Preserves Kidney Function
Renal fibrosis is a common pathological hallmark of progressive chronic kidney diseases, characterized by persistent inflammation, immune activation, and excessive extracellular matrix deposition.  Lectins play a role in modulating immune cell recruitment, amplifying pro-inflammatory signaling, and promoting fibrotic cellular phenotypes. Here, we demonstrate, in a population cohort of individuals with CKD, that the Galectin-3 is robustly expressed in diseased human kidneys and strongly correlates with clinical indices of renal dysfunction. Using the models of adenine induced nephropathy and unilateral ureteral occlusion in mice, we find that Galectin-3 upregulated in kidney collecting tubular cell after injury. Renal fibrosis was significantly reduced in Galectin-3-deficient kidneys, accompanied by lower levels of serum creatinine and blood urea nitrogen and decreased expression of myofibroblast marker a-SMA. RNA sequencing revealed that genes associated with the NF-?B signaling pathway were significantly enriched in the Galectin-3 knockout group. Treatment with GB1107, a selective Galectin-3 inhibitor, also markedly attenuated renal fibrosis, improved renal function and suppressed a-SMA expression. Taken together, our findings suggest that Galectin-3 promotes renal fibrosis through enhancement of inflammatory and fibrotic signaling pathways, and that targeting Galectin-3 may offer therapeutic benefit by preserving kidney function and attenuating interstitial fibrosis. Overall design: This study investigated the role of Galectin-3 in renal fibrosis and its therapeutic potential in chronic kidney disease using an integrated approach combining human CKD cohort analysis, genetic and pharmacological mouse models, and transcriptomic profiling. Galectin-3 expression and its association with renal dysfunction were examined in human kidney biopsies. Renal fibrosis was induced in mice using adenine-induced nephropathy and unilateral ureteral obstruction (UUO), and the functional role of Galectin-3 was assessed using Galectin-3–deficient mice. RNA sequencing was performed to identify Galectin-3–dependent inflammatory and fibrotic pathways. Finally, the therapeutic effects of the Galectin-3 inhibitor GB1107 were evaluated in murine models of renal fibrosis.