Pla2g7-KO Mouse

Pla2g7, encoding platelet activating factor acetyl hydrolase, is a pivotal enzyme in phospholipid metabolism [1,3,4,5,6,7]. It is involved in multiple biological processes related to lipid metabolism and immune regulation, which are crucial for maintaining normal physiological functions [1,2,3,5]. Gene knockout (KO) or conditional knockout (CKO) mouse models can be valuable for studying its functions in vivo.

In hepatocellular carcinoma (HCC), macrophage-specific Pla2g7 is highly expressed, correlating with poor prognosis and immunotherapy resistance. Inhibiting Pla2g7 reverses the immunosuppressive function of intratumoral macrophages and enhances immunotherapy response in HCC mouse models [1]. In pulmonary fibrosis, Pla2g7high macrophages promote fibroblast-to-myofibroblast transition (FMT), and pharmacological inhibition of Pla2g7 ameliorates pulmonary fibrosis in bleomycin-induced mice [2]. Deletion of Pla2g7 in mice shows decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health, suggesting that reduction of Pla2g7 may mediate the immunometabolic effects of caloric restriction [3]. In bladder cancer, knockdown of Pla2g7 inhibits PD-L1 expression, promotes CD8+ T-cell infiltration, and suppresses tumor growth. Suppressing Pla2g7 and anti-CTLA4 therapy have synergistic effects in syngeneic mouse models [5].

In conclusion, Pla2g7 plays significant roles in lipid metabolism and immune-related biological processes. Model-based research, especially KO/CKO mouse models, has revealed its implications in diseases like HCC, pulmonary fibrosis, age-related inflammation, and bladder cancer. Understanding Pla2g7 functions provides potential therapeutic targets for these diseases.

References:

1. Zhang, Feng, Liu, Wenfeng, Meng, Fansheng, Zhang, Si, Dong, Ling. 2024. Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma. In Journal for immunotherapy of cancer, 12, . doi:10.1136/jitc-2023-008094. https://pubmed.ncbi.nlm.nih.gov/38272562/

2. Wang, Junyi, Jiang, Manling, Xiong, Anying, Leung, Elaine Lai-Han, Li, Guoping. 2022. Integrated analysis of single-cell and bulk RNA sequencing reveals pro-fibrotic PLA2G7high macrophages in pulmonary fibrosis. In Pharmacological research, 182, 106286. doi:10.1016/j.phrs.2022.106286. https://pubmed.ncbi.nlm.nih.gov/35662628/

3. Spadaro, O, Youm, Y, Shchukina, I, Artyomov, M N, Dixit, V D. 2022. Caloric restriction in humans reveals immunometabolic regulators of health span. In Science (New York, N.Y.), 375, 671-677. doi:10.1126/science.abg7292. https://pubmed.ncbi.nlm.nih.gov/35143297/

4. Vermonden, Perrine, Martin, Manon, Glowacka, Katarzyna, Feron, Olivier, Larondelle, Yvan. 2024. Phospholipase PLA2G7 is complementary to GPX4 in mitigating punicic-acid-induced ferroptosis in prostate cancer cells. In iScience, 27, 109774. doi:10.1016/j.isci.2024.109774. https://pubmed.ncbi.nlm.nih.gov/38711443/

5. Peng, Ding, Yang, Wuping, Tang, Tianyu, Jing, Taile, Xia, Dan. 2025. PLA2G7 promotes immune evasion of bladder cancer through the JAK-STAT-PDL1 axis. In Cell death & disease, 16, 234. doi:10.1038/s41419-025-07593-1. https://pubmed.ncbi.nlm.nih.gov/40169540/

6. Morigny, Pauline, Kaltenecker, Doris, Zuber, Julia, Herzig, Stephan, Berriel Diaz, Mauricio. 2021. Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy. In Journal of cachexia, sarcopenia and muscle, 12, 1333-1351. doi:10.1002/jcsm.12758. https://pubmed.ncbi.nlm.nih.gov/34427055/

7. Liao, Yue, Badmann, Susann, Kraus, Fabian, Czogalla, Bastian, Burges, Alexander. 2023. PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer. In International journal of molecular sciences, 24, . doi:10.3390/ijms24010882. https://pubmed.ncbi.nlm.nih.gov/36614323/