Ptgis-KO Mouse

Ptgis, also known as prostaglandin I2 synthase, is a member of the cytochrome P450 family. It catalyzes the isomerization of prostaglandin H2 to prostacyclin, a potent vasodilator and inhibitor of platelet aggregation [9]. PTGIS is involved in metabolic pathways, arachidonic acid metabolism, steroid biosynthesis, and cancer pathways [3]. It also plays a role in fatty acid metabolism [2,6].

In patients with idiopathic pulmonary arterial hypertension (IPAH), rare loss-of-function variants in PTGIS were identified. These variants were associated with increased susceptibility to IPAH and a more significant pulmonary vascular response to iloprost, indicating a role in IPAH pathogenesis [1]. In endometriosis, hypoxia-hindered methylation of PTGIS in endometrial stromal cells accelerates the disease progression by inducing CD16-NK-cell differentiation [4]. In prostate cancer, rsRNA-28S regulates chemoresistance by targeting PTGIS [5]. In endometrial cancer, PTGIS affects the malignant biological behavior of the cancer cells [6]. In lung squamous cell carcinoma, PTGIS promotes cancer cell proliferation, migration, and invasion [7]. In liver fibrosis, DNA methylation of PTGIS enhances hepatic stellate cells activation and fibrogenesis, while overexpression of PTGIS inhibits this activation [8].

In conclusion, PTGIS is crucial in multiple biological processes and disease conditions. Its role in regulating prostacyclin production affects various physiological functions. Studies, especially those on loss-of-function variants and methylation-related changes, have revealed its significance in diseases like IPAH, endometriosis, and multiple types of cancer, providing potential therapeutic targets for these diseases.

References:

1. Wang, Xiao-Jian, Xu, Xi-Qi, Sun, Kai, Zhang, Xue, Jing, Zhi-Cheng. . Association of Rare PTGIS Variants With Susceptibility and Pulmonary Vascular Response in Patients With Idiopathic Pulmonary Arterial Hypertension. In JAMA cardiology, 5, 677-684. doi:10.1001/jamacardio.2020.0479. https://pubmed.ncbi.nlm.nih.gov/32236489/

2. Wu, Xiaoqing, Lu, Wenping, Xu, Chaojie, Wang, Ya'nan, Li, Chen. 2023. PTGIS May Be a Predictive Marker for Ovarian Cancer by Regulating Fatty Acid Metabolism. In Computational and mathematical methods in medicine, 2023, 2397728. doi:10.1155/2023/2397728. https://pubmed.ncbi.nlm.nih.gov/36785673/

3. Ding, Hui, Wang, Kai-Yun, Chen, Si-Yang, Guo, Kai-Wen, Qiu, Wen-Hong. 2023. Validating the role of PTGIS gene in colorectal cancer by bioinformatics analysis and in vitro experiments. In Scientific reports, 13, 16496. doi:10.1038/s41598-023-43289-2. https://pubmed.ncbi.nlm.nih.gov/37779109/

4. Peng, Haiyan, Weng, Lichun, Lei, Shating, Li, Mingqing, Zhao, Dong. 2022. Hypoxia-hindered methylation of PTGIS in endometrial stromal cells accelerates endometriosis progression by inducing CD16- NK-cell differentiation. In Experimental & molecular medicine, 54, 890-905. doi:10.1038/s12276-022-00793-1. https://pubmed.ncbi.nlm.nih.gov/35781537/

5. Qiao, Deqian, Liu, Yiling, Lei, Yunlong, Tang, Yishu, Zhang, Ying. . rRNA-Derived Small RNA rsRNA-28S Regulates the Chemoresistance of Prostate Cancer Cells by Targeting PTGIS. In Frontiers in bioscience (Landmark edition), 28, 102. doi:10.31083/j.fbl2805102. https://pubmed.ncbi.nlm.nih.gov/37258478/

6. Wang, Bo, Ge, Shuwen, Wang, Zihao, Leng, Hongrui, Ma, Xiaoxin. 2023. Analysis and experimental validation of fatty acid metabolism-related genes prostacyclin synthase (PTGIS) in endometrial cancer. In Aging, 15, 10322-10346. doi:10.18632/aging.205080. https://pubmed.ncbi.nlm.nih.gov/37796199/

7. Lei, Kai, Liang, Ruihao, Tan, Binghua, Lin, Huayue, Wang, Minghui. 2023. Effects of Lipid Metabolism-Related Genes PTGIS and HRASLS on Phenotype, Prognosis, and Tumor Immunity in Lung Squamous Cell Carcinoma. In Oxidative medicine and cellular longevity, 2023, 6811625. doi:10.1155/2023/6811625. https://pubmed.ncbi.nlm.nih.gov/36703911/

8. Pan, Xue-Yin, Yang, Yang, Meng, Hong-Wu, Meng, Xiao-Ming, Li, Jun. 2018. DNA Methylation of PTGIS Enhances Hepatic Stellate Cells Activation and Liver Fibrogenesis. In Frontiers in pharmacology, 9, 553. doi:10.3389/fphar.2018.00553. https://pubmed.ncbi.nlm.nih.gov/29892223/

9. Ershov, Pavel V, Mezentsev, Yuri V, Kopylov, Arthur T, Medvedev, Alexey E, Ivanov, Alexis S. 2019. Affinity Isolation and Mass Spectrometry Identification of Prostacyclin Synthase (PTGIS) Subinteractome. In Biology, 8, . doi:10.3390/biology8020049. https://pubmed.ncbi.nlm.nih.gov/31226805/