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 α-SMA. RNA sequencing revealed that genes associated with the NF-κB 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 α-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.