Ptafr-KO Mouse

Ptafr, the platelet-activating factor receptor, is a crucial component in various biological processes. Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator, and Ptafr is the receptor through which PAF exerts its pro-inflammatory, pro-coagulant, and angiogenic actions on the vasculature [4]. The PAF/Ptafr pathway is involved in multiple disease-related processes, such as inflammation, metastasis, and angiogenesis [5,6]. Genetic models are valuable for studying Ptafr's functions.

In a TP53/CDKN2A double-knockout gastroesophageal junction organoid model, inactivation of these tumor suppressor genes up-regulated PTAF and its receptor PTAFR. Abrogation of PTAFR by siRNA knockdown or a pharmacologic inhibitor reduced proliferation and proneoplastic features both in vitro and in vivo, revealing its role in promoting tumorigenesis [1]. In an atherosclerosis study, bioinformatics analysis and validation experiments identified PTAFR as a key gene regulating neutrophil extracellular traps (NETs) formation, impacting the progression and prognosis of atherosclerosis [2]. In cardiac fibrosis research, knockdown of PTAFR affected the pro-fibrotic collagen production mediated by the lncRNA PFL, and its overexpression also led to collagen production [3].

In conclusion, Ptafr plays essential roles in tumorigenesis, atherosclerosis, and cardiac fibrosis. Gene-knockout models have been instrumental in uncovering these functions, providing insights into the molecular mechanisms underlying these diseases and suggesting Ptafr as a potential therapeutic target for related disease treatment.

References:

1. Zhao, Hua, Cheng, Yulan, Kalra, Andrew, Lin, De-Chen, Meltzer, Stephen J. 2022. Generation and multiomic profiling of a TP53/CDKN2A double-knockout gastroesophageal junction organoid model. In Science translational medicine, 14, eabq6146. doi:10.1126/scitranslmed.abq6146. https://pubmed.ncbi.nlm.nih.gov/36449602/

2. Ye, Chaowen, Zhao, Yunli, Yu, Wei, Huang, Rongzhong, Hu, Tianyang. 2024. Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progression. In Human genomics, 18, 139. doi:10.1186/s40246-024-00708-3. https://pubmed.ncbi.nlm.nih.gov/39709510/

3. Leisegang, Matthias S. 2018. LET's sponge: How the lncRNA PFL promotes cardiac fibrosis. In Theranostics, 8, 874-877. doi:10.7150/thno.23364. https://pubmed.ncbi.nlm.nih.gov/29463987/

4. Bhosle, Vikrant K, Rivera, José Carlos, Zhou, Tianwei Ellen, Ribeiro-da-Silva, Alfredo, Chemtob, Sylvain. 2016. Nuclear localization of platelet-activating factor receptor controls retinal neovascularization. In Cell discovery, 2, 16017. doi:10.1038/celldisc.2016.17. https://pubmed.ncbi.nlm.nih.gov/27462464/

5. Cao, Linna, Zhang, Yiwei, Mi, Jinxia, Pan, Zhiqiang, Peng, Peike. 2022. α-Hederin inhibits the platelet activating factor-induced metastasis of HCC cells through disruption of PAF/PTAFR axis cascaded STAT3/MMP-2 expression. In Pharmacological research, 178, 106180. doi:10.1016/j.phrs.2022.106180. https://pubmed.ncbi.nlm.nih.gov/35288308/

6. Hou, Tianhui, Lou, Yan, Li, Shichang, Li, Zhenxi, Xiao, Jianru. 2018. Kadsurenone is a useful and promising treatment strategy for breast cancer bone metastases by blocking the PAF/PTAFR signaling pathway. In Oncology letters, 16, 2255-2262. doi:10.3892/ol.2018.8935. https://pubmed.ncbi.nlm.nih.gov/30008927/