LGALS3BP, also known as Galectin 3-binding protein or 90K, is a multifunctional glycoprotein. It is involved in multiple biological processes such as immunity, cell migration, and angiogenesis. It has been linked to pathways like the TGF-β1 signaling pathway, extracellular matrix-related processes, and PI3K/AKT pathway, playing a significant role in various physiological and pathological conditions [1,2,3]. Genetic models, like knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in understanding its functions.

In hepatic fibrosis and hepatocarcinogenesis, LGALS3BP-knockout in hepatocytes downregulated TGF-β1 signaling and attenuated CCl4-induced fibrosis, hindering hepatocarcinogenesis as well. This shows that LGALS3BP plays a crucial role in these diseases by controlling the TGF-β1 signaling pathway [1]. In colitis and colon tumorigenesis, Lgals3bp-/-mice were highly susceptible to colitis and colon tumorigenesis, with enhanced inflammatory responses due to the activation of NF-κB, indicating that Lgals3bp suppresses these through the down-regulation of the TAK1-NF-κB-cytokine axis [4].

In conclusion, LGALS3BP has diverse functions in different biological processes and diseases. Model-based research, especially using KO/CKO mouse models, has revealed its role in hepatic fibrosis, hepatocarcinogenesis, colitis, and colon tumorigenesis. These findings suggest that LGALS3BP could be a potential therapeutic target for these diseases.

References:

1. Kim, Dae-Hwan, Sung, Minjeong, Park, Myong-Suk, Cho, Sang-Hee, Chung, Ik-Joo. 2024. Galectin 3-binding protein (LGALS3BP) depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1 (TGF-β1) availability and inhibits hepatocarcinogenesis. In Cancer communications (London, England), 44, 1106-1129. doi:10.1002/cac2.12600. https://pubmed.ncbi.nlm.nih.gov/39073023/

2. Kyrousi, Christina, O'Neill, Adam C, Brazovskaja, Agnieska, Robertson, Stephen P, Cappello, Silvia. 2021. Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity. In Nature communications, 12, 6298. doi:10.1038/s41467-021-26447-w. https://pubmed.ncbi.nlm.nih.gov/34728600/

3. Zhao, Chenyang, Liu, Yusen, Meng, Jiayu, Li, Na, Hou, Shengping. . LGALS3BP in Microglia Promotes Retinal Angiogenesis Through PI3K/AKT Pathway During Hypoxia. In Investigative ophthalmology & visual science, 63, 25. doi:10.1167/iovs.63.8.25. https://pubmed.ncbi.nlm.nih.gov/35895036/

4. Cho, Sang-Hee, Shim, Hyun-Jeong, Park, Mi-Ra, Sun, Eun-Gene, Chung, Ik-Joo. 2021. Lgals3bp suppresses colon inflammation and tumorigenesis through the downregulation of TAK1-NF-κB signaling. In Cell death discovery, 7, 65. doi:10.1038/s41420-021-00447-7. https://pubmed.ncbi.nlm.nih.gov/33824294/