Fgl2, also known as fibrinogen-like protein 2, is a multifunctional protein. It belongs to the thrombospondin family and is involved in regulating the activity of immune cells, tumor cells, and prothrombin activity. It has a significant impact on various biological processes such as immunity, coagulation, and is associated with pathways like CXCL9/10-CXCR3 chemokine axis, CD16/SyK/PI3K/HIF1α pathways, and PI3K/NF-κB pathway [1,2,3,4,6,7]. Genetic models, especially knockout (KO) mouse models, have been crucial in understanding its functions.

In glioma, Fgl2 promotes tumor cell stem-like phenotypes, immunosuppression, and malignant progression. T cells expressing Fgl2-specific single-chain variable fragments can recruit tumor-specific brain-resident memory T cells, which prevent glioblastoma recurrence [1,3]. In melanoma and ovarian cancer models, absence of Fgl2 leads to a more activated tumor microenvironment and prolonged survival, indicating Fgl2 promotes tumor growth and attenuates infiltration of activated immune cells [5]. In fulminant viral hepatitis, neutrophil-specific Fgl2 promotes the formation of neutrophil extracellular traps, which exacerbate liver injury [4]. Also, in maternal inflammation-induced blood-brain barrier damage, Fgl2 deficiency alleviates the disruption by inhibiting PI3K/NF-κB mediated oxidative stress [6].

In conclusion, Fgl2 plays essential roles in immunity, coagulation, and tumor-related processes. The use of Fgl2 KO mouse models has revealed its functions in diseases such as glioma, melanoma, ovarian cancer, fulminant viral hepatitis, and maternal-inflammation-induced brain damage. Understanding Fgl2 provides insights into disease mechanisms and potential therapeutic targets for these conditions.

References:

1. Ma, Xiaoyu, Zhu, Hongtao, Cheng, Lidong, Shu, Kai, Zhang, Suojun. 2022. Targeting FGL2 in glioma immunosuppression and malignant progression. In Frontiers in oncology, 12, 1004700. doi:10.3389/fonc.2022.1004700. https://pubmed.ncbi.nlm.nih.gov/36313679/

2. Chen, Jiongming, Wu, Lei, Li, Yongsheng. 2024. FGL1 and FGL2: emerging regulators of liver health and disease. In Biomarker research, 12, 53. doi:10.1186/s40364-024-00601-0. https://pubmed.ncbi.nlm.nih.gov/38816776/

3. Zhao, Qingnan, Hu, Jiemiao, Kong, Lingyuan, Heimberger, Amy B, Li, Shulin. 2023. FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells. In Nature communications, 14, 735. doi:10.1038/s41467-023-36430-2. https://pubmed.ncbi.nlm.nih.gov/36759517/

4. Li, Xitang, Gao, Qiang, Wu, Wenhui, Ning, Qin, Wang, Xiaojing. 2022. FGL2-MCOLN3-Autophagy Axis-Triggered Neutrophil Extracellular Traps Exacerbate Liver Injury in Fulminant Viral Hepatitis. In Cellular and molecular gastroenterology and hepatology, 14, 1077-1101. doi:10.1016/j.jcmgh.2022.07.014. https://pubmed.ncbi.nlm.nih.gov/35926777/

5. Galpin, Kristianne J C, Rodriguez, Galaxia M, Maranda, Vincent, Ardolino, Michele, Vanderhyden, Barbara C. 2024. FGL2 promotes tumour growth and attenuates infiltration of activated immune cells in melanoma and ovarian cancer models. In Scientific reports, 14, 787. doi:10.1038/s41598-024-51217-1. https://pubmed.ncbi.nlm.nih.gov/38191799/

6. Huang, Lianjing, Zhan, Di, Xing, Ying, Zhang, Cai, Luo, Xiaoping. 2023. FGL2 deficiency alleviates maternal inflammation-induced blood-brain barrier damage by blocking PI3K/NF-κB mediated endothelial oxidative stress. In Frontiers in immunology, 14, 1157027. doi:10.3389/fimmu.2023.1157027. https://pubmed.ncbi.nlm.nih.gov/37051251/

7. Yan, Jun, Zhao, Qingnan, Wang, Jian, Heimberger, Amy B, Li, Shulin. 2021. FGL2-wired macrophages secrete CXCL7 to regulate the stem-like functionality of glioma cells. In Cancer letters, 506, 83-94. doi:10.1016/j.canlet.2021.02.021. https://pubmed.ncbi.nlm.nih.gov/33676940/