Ptgs2-KO Mouse

Ptgs2, also known as Prostaglandin-endoperoxide Synthase 2 or Cyclooxygenase 2 (COX2), is the rate-limiting enzyme in the production of prostaglandins (PGs). It is involved in the prostaglandin synthesis pathway and plays a crucial role in various physiological and pathophysiological processes such as inflammation, pain, and fever [1,2,3,5,6,7,8,9,10]. Prostaglandin E2 (PGE2), the main product of Ptgs2 expression and activation, promotes diverse tissue-specific effects [1]. Genetic models, especially KO/CKO mouse models, can be valuable in studying its functions.

In type 1 diabetes mellitus, the PTGS2/COX2-PGE2 signaling cascade shows controversial effects on pancreatic islet cells, with PGE2 being both a cause and consequence of inflammation [1]. In human coronary artery atherosclerosis, Ptgs2 is upregulated in advanced stages, and it might be the hub gene in this disease, with ferroptosis and pyroptosis possibly regulated by Ptgs2-related pathways [2]. In mice, endothelial ROBO4 downregulates Ptgs2 expression, and Robo4-deficiency exacerbates Ptgs2-associated inflammatory diseases, like arthritis, edema, and pain [3]. In colorectal cancer, Ptgs2-positive patients have an increased risk of tumor recurrence and poorer colorectal-cancer-specific survival [4]. In chronic spontaneous urticaria, Ptgs2 may be a potential immune and inflammation regulator, and targeting it offers a new treatment perspective [5]. In the oviduct, Ptgs2 plays an essential role in fertilization and early embryo development, though its regulation in oviductal functions is not fully understood [6]. In intervertebral disc degeneration, the ERBB2-PTGS2 axis regulates nucleus pulposus cell senescence, with ERBB2 overexpression alleviating IDD by inhibiting PTGS2 [7]. In colorectal cancer cells, the transcription factor RUNX1 upregulates Ptgs2, promoting cell growth, migration, and invasion [8]. In nasopharyngeal carcinoma, miR-26a-5p suppresses tumor progression by inhibiting Ptgs2 expression [9]. In preeclampsia, PTGS2 silencing reverses the promoting effect of LPS on trophoblast invasion and inflammation [10].

In conclusion, Ptgs2 is essential in multiple biological processes, especially those related to inflammation and tissue-specific responses. The use of KO/CKO mouse models and other functional studies has revealed its role in diseases such as diabetes, atherosclerosis, various cancers, chronic spontaneous urticaria, and preeclampsia. Understanding Ptgs2 function provides potential therapeutic targets for these diseases.

References:

1. Martín-Vázquez, Eugenia, Cobo-Vuilleumier, Nadia, López-Noriega, Livia, Lorenzo, Petra I, Gauthier, Benoit R. 2023. The PTGS2/COX2-PGE2 signaling cascade in inflammation: Pro or anti? A case study with type 1 diabetes mellitus. In International journal of biological sciences, 19, 4157-4165. doi:10.7150/ijbs.86492. https://pubmed.ncbi.nlm.nih.gov/37705740/

2. Zhou, Yaqing, Zhou, Hanxiao, Hua, Lei, He, Shu, Jia, Enzhi. 2021. Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis. In Free radical biology & medicine, 171, 55-68. doi:10.1016/j.freeradbiomed.2021.05.009. https://pubmed.ncbi.nlm.nih.gov/33974977/

3. Tanaka, Masato, Shirakura, Keisuke, Takayama, Yui, Takayama, Kazuo, Okada, Yoshiaki. 2024. Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases. In Communications biology, 7, 599. doi:10.1038/s42003-024-06317-z. https://pubmed.ncbi.nlm.nih.gov/38762541/

4. Kunzmann, Andrew T, Murray, Liam J, Cardwell, Chris R, McMenamin, Una C, Cantwell, Marie M. 2013. PTGS2 (Cyclooxygenase-2) expression and survival among colorectal cancer patients: a systematic review. In Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 22, 1490-7. doi:10.1158/1055-9965.EPI-13-0263. https://pubmed.ncbi.nlm.nih.gov/23810915/

5. Chen, Yihui, Jian, Xingxing, Zhu, Lei, Xiong, Feng, Li, Jie. 2024. PTGS2: A potential immune regulator and therapeutic target for chronic spontaneous urticaria. In Life sciences, 344, 122582. doi:10.1016/j.lfs.2024.122582. https://pubmed.ncbi.nlm.nih.gov/38514006/

6. Anamthathmakula, Prashanth, Winuthayanon, Wipawee. . Prostaglandin-Endoperoxide Synthase 2 (PTGS2) in the Oviduct: Roles in Fertilization and Early Embryo Development. In Endocrinology, 162, . doi:10.1210/endocr/bqab025. https://pubmed.ncbi.nlm.nih.gov/33539521/

7. Li, Zhao-Cheng, An, Fu. 2023. ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells. In BMC musculoskeletal disorders, 24, 504. doi:10.1186/s12891-023-06625-1. https://pubmed.ncbi.nlm.nih.gov/37340393/

8. Zheng, Weiwei, Guo, Yingchang, Kahar, Aihemaiti, Zhang, Chao, Zhu, Yuanzeng. 2024. RUNX1-induced upregulation of PTGS2 enhances cell growth, migration and invasion in colorectal cancer cells. In Scientific reports, 14, 11670. doi:10.1038/s41598-024-60296-z. https://pubmed.ncbi.nlm.nih.gov/38778047/

9. Cai, Binlin, Qu, Xiu, Kan, Dan, Luo, Yi. 2022. miR-26a-5p suppresses nasopharyngeal carcinoma progression by inhibiting PTGS2 expression. In Cell cycle (Georgetown, Tex.), 21, 618-629. doi:10.1080/15384101.2022.2030168. https://pubmed.ncbi.nlm.nih.gov/35073820/

10. Li, Ruolan, Xie, Jirong, Xu, Wei, Lin, Huimin, Huang, Wanjun. 2022. LPS-induced PTGS2 manipulates the inflammatory response through trophoblast invasion in preeclampsia via NF-κB pathway. In Reproductive biology, 22, 100696. doi:10.1016/j.repbio.2022.100696. https://pubmed.ncbi.nlm.nih.gov/36327673/