Panx1, or pannexin 1, is a ubiquitously expressed protein that forms an ATP-releasing membrane channel. It is involved in multiple biological processes, such as inflammation, blood pressure regulation, and is associated with pathways like the Akt-FOXO1 pathway in hepatocytes and P2Y receptor-mediated regulation in various cell types. Genetic models, especially knockout (KO) mouse models, have been crucial in studying its functions [1-10].

In cardiomyocytes, deletion of Panx1 (Panx1MyHC6 mice) increased glycolytic metabolism and protected against cardiac hypertrophy in non-ischemic heart failure, likely by reducing immune cell recruitment [1]. In the liver, global or hepatic knockdown of Panx1 in mice led to disturbed glucolipid metabolism, while overexpression ameliorated it, with Panx1-mediated ATP release regulating gluconeogenesis and lipogenesis [2]. In mice, capillary-associated microglia regulated vascular structure and function through the PANX1-P2RY12 coupling, as seen in P2RY12-/-and PANX1-/-mice [3]. Global or neuron-specific Panx1 deletion in mice decreased pain thresholds in experimental plantar inflammatory pain, indicating Panx1's role in enhancing pain sensitivity [4]. In HCC, high Panx1 expression was associated with poor prognosis, and overexpression promoted invasion and migration through EMT modulation in vivo and in vitro [5]. In Panx1-null mice, long-term spatial reference memory was deficient, with both astrocyte and neuronal Panx1 contributing to long-term spatial memory consolidation [6,7]. In pancreatic adenocarcinoma, high Panx1 expression was associated with poor prognosis and immune infiltration [8]. In astrocytes, ethanol-induced opening of Panx1 channels led to dysfunction and damage [9].

In summary, Panx1 is a key protein involved in diverse biological processes, including metabolism, pain sensitivity, memory, and immune-related functions. The use of Panx1 KO/CKO mouse models has revealed its significant roles in diseases such as heart failure, metabolic disorders, inflammatory pain, cancer, and alcohol-induced astrocyte damage, providing valuable insights into disease mechanisms and potential therapeutic targets.

References:

1. Pavelec, Caitlin M, Young, Alexander P, Luviano, Hannah L, Wolf, Matthew J, Leitinger, Norbert. 2024. Cardiomyocyte PANX1 Controls Glycolysis and Neutrophil Recruitment in Hypertrophy. In Circulation research, 135, 503-517. doi:10.1161/CIRCRESAHA.124.324650. https://pubmed.ncbi.nlm.nih.gov/38957990/

2. Hu, Cheng-Qing, Hou, Tao, Xiang, Rui, Chi, Yu-Jing, Yang, Ji-Chun. 2024. PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis. In Military Medical Research, 11, 41. doi:10.1186/s40779-024-00543-6. https://pubmed.ncbi.nlm.nih.gov/38937853/

3. Bisht, Kanchan, Okojie, Kenneth A, Sharma, Kaushik, Kuan, Chia-Yi, Eyo, Ukpong B. 2021. Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice. In Nature communications, 12, 5289. doi:10.1038/s41467-021-25590-8. https://pubmed.ncbi.nlm.nih.gov/34489419/

4. Xing, Qu, Cibelli, Antonio, Yang, Greta Luyuan, Guan, Fang-Xia, Spray, David C. 2024. Neuronal Panx1 drives peripheral sensitization in experimental plantar inflammatory pain. In Military Medical Research, 11, 27. doi:10.1186/s40779-024-00525-8. https://pubmed.ncbi.nlm.nih.gov/38685116/

5. Shi, Guangjun, Liu, Chuanliang, Yang, Yiming, Li, Hao, Zhong, Lin. 2019. Panx1 promotes invasion-metastasis cascade in hepatocellular carcinoma. In Journal of Cancer, 10, 5681-5688. doi:10.7150/jca.32986. https://pubmed.ncbi.nlm.nih.gov/31737105/

6. Obot, Price, Subah, Galadu, Schonwald, Antonia, Stanton, Patric K, Scemes, Eliana. . Astrocyte and Neuronal Panx1 Support Long-Term Reference Memory in Mice. In ASN neuro, 15, 17590914231184712. doi:10.1177/17590914231184712. https://pubmed.ncbi.nlm.nih.gov/37365910/

7. Obot, Price, Subah, Galadu, Schonwald, Antonia, Stanton, Patric K, Scemes, Eliana. 2023. Astrocyte and neuronal Panx1 support long-term reference memory in mice. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.01.16.524236. https://pubmed.ncbi.nlm.nih.gov/36711845/

8. Bao, Lingling, Sun, Kai, Zhang, Xuede. . PANX1 is a potential prognostic biomarker associated with immune infiltration in pancreatic adenocarcinoma: A pan-cancer analysis. In Channels (Austin, Tex.), 15, 680-696. doi:10.1080/19336950.2021.2004758. https://pubmed.ncbi.nlm.nih.gov/34796785/

9. Gómez, Gonzalo I, Alvear, Tanhia F, Roa, Daniela A, Ortíz, Fernando C, Orellana, Juan A. 2024. Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage. In Biological research, 57, 15. doi:10.1186/s40659-024-00493-2. https://pubmed.ncbi.nlm.nih.gov/38576018/