Tbxa2r-KO Mouse

Tbxa2r, encoding the α isoform of the thromboxane receptor (TPα receptor), is a G-protein-coupled receptor. It participates in tissue inflammation, platelet aggregation, and is involved in multiple biological pathways [1,3,4]. Platelet activity regulation by Tbxa2r is crucial for thrombus formation, and its study via genetic models can reveal its function in various physiological and pathological conditions.

Genetic deletion of Tbxa2r protected mice from bleomycin-induced lung fibrosis, indicating its role in linking oxidative stress to fibroblast activation during lung fibrosis [2]. In human studies, the TBXA2R rs4523 G allele was associated with decreased susceptibility to Kawasaki disease in a southern Chinese population [3]. Also, certain TBXA2R gene polymorphisms were related to an increased risk of ischemic stroke [5], and some variants in the gene were associated with an increased risk of aspirin-induced upper gastrointestinal bleeding in cardiovascular disease patients using low-dose aspirin [6]. A single nucleotide polymorphism in the TBXA2R gene was associated with increased metastasis in multiple primary cancers, suggesting the clinical applicability of TBXA2R antagonists [7].

In conclusion, Tbxa2r is essential in regulating platelet activity, tissue inflammation, and is involved in multiple disease conditions such as pulmonary fibrosis, Kawasaki disease, ischemic stroke, upper gastrointestinal bleeding, and cancer metastasis. Gene knockout and human genetic studies of Tbxa2r have provided valuable insights into its role in these diseases, potentially guiding the development of new therapeutic strategies.

References:

1. Mundell, Stuart James, Mumford, Andrew. 2018. TBXA2R gene variants associated with bleeding. In Platelets, 29, 739-742. doi:10.1080/09537104.2018.1499888. https://pubmed.ncbi.nlm.nih.gov/30089223/

2. Suzuki, Toshio, Kropski, Jonathan A, Chen, Jingyuan, Blackwell, Timothy S, West, James D. . Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis. In American journal of respiratory and critical care medicine, 206, 596-607. doi:10.1164/rccm.202106-1503OC. https://pubmed.ncbi.nlm.nih.gov/35728047/

3. Che, Di, Pi, Lei, Xu, Yufen, Zhang, Li, Gu, Xiaoqiong. 2018. TBXA2R rs4523 G allele is associated with decreased susceptibility to Kawasaki disease. In Cytokine, 111, 216-221. doi:10.1016/j.cyto.2018.08.029. https://pubmed.ncbi.nlm.nih.gov/30179800/

4. Buroker, Norman E. 2014. Regulatory SNPs and transcriptional factor binding sites in ADRBK1, AKT3, ATF3, DIO2, TBXA2R and VEGFA. In Transcription, 5, e964559. doi:10.4161/21541264.2014.964559. https://pubmed.ncbi.nlm.nih.gov/25483406/

5. Liang, Xuesong, Zhou, You, Li, Shuoxi. 2020. Association of TBXA2R, P2Y12 and ADD1 genes polymorphisms with ischemic stroke susceptibility: A metaanalysis. In Clinical and investigative medicine. Medecine clinique et experimentale, 43, E33-43. doi:10.25011/cim.v43i3.34597. https://pubmed.ncbi.nlm.nih.gov/32971583/

6. Forgerini, Marcela, Gini, Ana Luísa Rodriguez, Lemos, Isabele Held, Valentini, Sandro Roberto, Mastroianni, Patrícia de Carvalho. 2024. The Impact of TBXA2R Gene Variants on the Risk of Aspirin-Induced Upper Gastrointestinal Bleeding: A Case-Control Study. In Hospital pharmacy, 59, 666-676. doi:10.1177/00185787241269111. https://pubmed.ncbi.nlm.nih.gov/39465093/

7. Pulley, Jill M, Jerome, Rebecca N, Ogletree, Martin L, Holroyd, Kenneth J, Cook, Rebecca S. . Motivation for Launching a Cancer Metastasis Inhibition (CMI) Program. In Targeted oncology, 13, 61-68. doi:10.1007/s11523-017-0542-1. https://pubmed.ncbi.nlm.nih.gov/29218624/