Aqp1-KO Mouse

Aqp1, belonging to the aquaporin family of water channel proteins, is characterized by two NPA (Asp-Pro-Ala) motifs and is present in almost all organs and tissues. It is mainly responsible for water molecule transport, and some studies suggest it may also be involved in the transport of small volatile molecules like CO2 [2,4]. Aqp1 is crucial in maintaining normal physiological functions related to water balance and is potentially involved in multiple signaling pathways. Genetic models, such as gene knockout (KO) mouse models, can be used to study its functions.

In endothelial cells, Aqp1 differentially orchestrates extracellular hydrogen peroxide (H2O2)-induced cellular senescence. In proliferating endothelial cells, it is vital for angiogenic capacity, while its disruption leads to senescence and impaired angiogenesis. In senescent endothelial cells, knocking down Aqp1 or blocking it can rescue the excess H2O2-induced cellular senescence phenotype and metabolic dysfunction, ameliorating angiogenic incompetence. Mechanistically, Aqp1 facilitates H2O2 transmembrane transport, influencing oxidant-sensitive kinases and signaling pathways related to endothelial cell senescence and angiogenesis [1]. In peritoneal dialysis patients, a common Aqp1 promoter variant rs2075574 is associated with decreased peritoneal ultrafiltration and an increased risk of death or technique failure. This variant reduces Aqp1 promoter activity, aquaporin-1 expression, and glucose-driven osmotic water transport [3].

In conclusion, Aqp1 is essential for water transport and maintaining normal physiological functions. Through model-based research, it has been revealed to play significant roles in endothelial cell senescence, angiogenesis, and peritoneal dialysis-related outcomes. The study of Aqp1 using KO mouse models and other functional studies helps to understand its functions in specific biological processes and disease conditions, providing potential therapeutic targets for age-related cardiovascular diseases and improving peritoneal dialysis outcomes [1,3].

References:

1. Shabanian, Khatereh, Shabanian, Taraneh, Karsai, Gergely, Beer, Jürg H, Saeedi Saravi, Seyed Soheil. 2024. AQP1 differentially orchestrates endothelial cell senescence. In Redox biology, 76, 103317. doi:10.1016/j.redox.2024.103317. https://pubmed.ncbi.nlm.nih.gov/39180980/

2. Magni, Fulvio, Chinello, Clizia, Raimondo, Francesca, Kienle, Marzia Galli, Pitto, Marina. . AQP1 expression analysis in human diseases: implications for proteomic characterization. In Expert review of proteomics, 5, 29-43. doi:10.1586/14789450.5.1.29. https://pubmed.ncbi.nlm.nih.gov/18282122/

3. Morelle, Johann, Marechal, Céline, Yu, Zanzhe, Davies, Simon, Devuyst, Olivier. . AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis. In The New England journal of medicine, 385, 1570-1580. doi:10.1056/NEJMoa2034279. https://pubmed.ncbi.nlm.nih.gov/34670044/

4. Cooper, Gordon J, Zhou, Yuehan, Bouyer, Patrice, Grichtchenko, Irina I, Boron, Walter F. . Transport of volatile solutes through AQP1. In The Journal of physiology, 542, 17-29. doi:. https://pubmed.ncbi.nlm.nih.gov/12096045/