Fgb-KO Mouse

Fgb, which encodes the Bβ chain of fibrinogen, is a crucial gene. Fibrinogen, a hexameric plasmatic glycoprotein composed of pairs of three chains (Aα, Bβ, and γ), plays an essential role in hemostasis. Conversion of fibrinogen to insoluble polymer fibrin provides structural stability, strength, and adhesive surfaces for blood clots. It also has antithrombotic properties after fibrin clot formation. Moreover, fibrinogen and fibrin are involved in multiple biological processes such as fibrinolysis, matrix physiology, wound healing, inflammation, infection, cell interaction, angiogenesis, tumour growth, and metastasis [1].

In congenital fibrinogen deficiencies, mutations in Fgb can lead to variable clinical manifestations, from asymptomatic conditions to life-threatening bleeds or thromboembolic events [1]. In renal cell carcinoma (RCC), SIRT1 downregulates FGB expression to inhibit tumorigenesis by destabilizing STAT3, suggesting an important role of Fgb in RCC progression [2]. Plasma exosomal FGB, along with FGG, may serve as potential biomarkers to distinguish benign from malignant pulmonary nodules [3]. In breast cancer, FGB is highly expressed, and miR-877-5p can inhibit epithelial-mesenchymal transformation, cell proliferation, and invasion of breast cancer cells by downregulating FGB [4]. miR-139-5p suppresses proliferation and angiogenesis of intracranial aneurysm via FGB [5]. Also, circ_16601 promotes lung adenocarcinoma (LUAD) progression through the miR-5580-5p/FGB axis [6]. A novel homozygous missense mutation in FGB (p.Cys241Tyr) was found in a male patient with congenital afibrinogenemia and recurrent intracranial bleeding [7].

In conclusion, Fgb is essential for normal hemostasis and is involved in a variety of biological processes. Its dysregulation is associated with multiple diseases, including bleeding and thrombotic disorders, and various cancers. The study of Fgb through genetic models could potentially provide insights into the pathogenesis of these diseases and offer new therapeutic targets.

References:

1. Simurda, Tomas, Brunclikova, Monika, Asselta, Rosanna, Stasko, Jan, Kubisz, Peter. 2020. Genetic Variants in the FGB and FGG Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype. In International journal of molecular sciences, 21, . doi:10.3390/ijms21134616. https://pubmed.ncbi.nlm.nih.gov/32610551/

2. Chen, Yanbing, Zhu, Ying, Sheng, Yanling, Zhang, Shouhua, Xiang, Tianxin. 2019. SIRT1 downregulated FGB expression to inhibit RCC tumorigenesis by destabilizing STAT3. In Experimental cell research, 382, 111466. doi:10.1016/j.yexcr.2019.06.011. https://pubmed.ncbi.nlm.nih.gov/31201813/

3. Kuang, Muyu, Peng, Yizhou, Tao, Xiaoting, Sun, Yihua, Zhang, Huibiao. 2019. FGB and FGG derived from plasma exosomes as potential biomarkers to distinguish benign from malignant pulmonary nodules. In Clinical and experimental medicine, 19, 557-564. doi:10.1007/s10238-019-00581-8. https://pubmed.ncbi.nlm.nih.gov/31576477/

4. Liu, Haixia, Xiang, Lili, Mei, Yu. 2022. miR-877-5p Inhibits Epithelial Mesenchymal Transformation of Breast Cancer Cells by Targeting FGB. In Disease markers, 2022, 4882375. doi:10.1155/2022/4882375. https://pubmed.ncbi.nlm.nih.gov/36438895/

5. Jin, Tao, Chen, Gong, An, Qingzhu, Zhou, Bing, Leng, Bing. 2022. miR-139-5p Suppresses Proliferation and Angiogenesis of Intracranial Aneurysm via FGB. In Journal of healthcare engineering, 2022, 5824327. doi:10.1155/2022/5824327. https://pubmed.ncbi.nlm.nih.gov/35469231/

6. Zhou, Jie, Li, Peiwei, Zhao, Xiaogang, Li, Yuliang, Tian, Zhongxian. 2023. Circ_16601 facilitates Hippo pathway signaling via the miR-5580-5p/FGB axis to promote my-CAF recruitment in the TME and LUAD progression. In Respiratory research, 24, 276. doi:10.1186/s12931-023-02566-4. https://pubmed.ncbi.nlm.nih.gov/37953225/

7. Zdziarska, Joanna, Wypasek, Ewa, Iwaniec, Teresa, Neerman-Arbez, Marguerite, Undas, Anetta. 2020. Afibrinogenemia caused by a novel homozygous missense mutation, FGB p.Cys241Tyr, in a male patient with recurrent intracranial bleeding: case report and review of literature. In Haemophilia : the official journal of the World Federation of Hemophilia, 27, 26-32. doi:10.1111/hae.14211. https://pubmed.ncbi.nlm.nih.gov/33245842/