Lgals3, also known as Galectin-3, is a β-galactoside-binding protein. It binds proteins in carbohydrate-dependent and-independent ways and is involved in multiple biological activities such as cell growth, apoptosis, differentiation, angiogenesis, inflammation, fibrosis, and host defense [3]. It has been associated with various signaling pathways, though the exact pathways are context-dependent across different tissues and disease states.

In kidney stone research, knockout of Lgals3 in in vivo models significantly reduces calcium oxalate (CaOx) crystal deposition and renal fibrosis. Lgals3 deficiency also decreases the glycolytic rate and lactate production during CaOx deposition, inhibits histone lactylation of H3K18la, and inhibits the transcription, activation, and expression of FGFR4. This suggests Lgals3 plays a key role in CaOx stone formation and kidney injury by interacting with PKM2 and promoting H3K18la-mediated gene transcription and activation [1]. In glaucoma mouse models, genetic and pharmacologic targeting of Galectin-3 (Lgals3) ameliorated retinal ganglion cell (RGC) degeneration, indicating its role in glaucoma-related neurodegeneration [2].

In summary, Lgals3 is involved in multiple biological functions, with its role being elucidated through gene knockout models in diseases like kidney stone formation and glaucoma. These models have been crucial in revealing its contribution to pathological processes, potentially paving the way for new therapeutic strategies in these disease areas.

References:

1. Ye, Zehua, Sun, Yushi, Yang, Songyuan, Zhou, Xiangjun, Cheng, Fan. 2025. Lgals3 Promotes Calcium Oxalate Crystal Formation and Kidney Injury Through Histone Lactylation-Mediated FGFR4 Activation. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2413937. doi:10.1002/advs.202413937. https://pubmed.ncbi.nlm.nih.gov/39903812/

2. Margeta, Milica A, Yin, Zhuoran, Madore, Charlotte, Chen, Dong Feng, Butovsky, Oleg. 2022. Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma. In Immunity, 55, 1627-1644.e7. doi:10.1016/j.immuni.2022.07.014. https://pubmed.ncbi.nlm.nih.gov/35977543/

3. Dong, Rui, Zhang, Min, Hu, Qunying, Zheng, Yijie, Yuan, Hui. 2017. Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy (Review). In International journal of molecular medicine, 41, 599-614. doi:10.3892/ijmm.2017.3311. https://pubmed.ncbi.nlm.nih.gov/29207027/