Aqp1-KO Mouse

Aqp1, belonging to the aquaporin family of water channel proteins, is characterized by sequence similarity and two NPA motifs. It is mainly responsible for transporting water molecules, and is expressed in almost all organs and tissues [2]. Aqp1 has been implicated in multiple physiological and pathological processes, with its role in water transport being crucial for maintaining normal physiological functions. Genetic models, such as knockout mouse models, are valuable for studying its functions.

In endothelial cells, Aqp1 differentially orchestrates extracellular hydrogen peroxide (H2O2)-induced cellular senescence. Disrupting Aqp1 in proliferating endothelial cells leads to morphological and mitochondrial changes, senescence, and impaired angiogenesis. Conversely, knocking down Aqp1 in senescent endothelial cells rescues the H2O2 -induced senescence phenotype and metabolic dysfunction, improving angiogenic incompetence. Mechanistically, Aqp1 facilitates H2O2 transmembrane transport, affecting oxidant-sensitive kinases and relevant signaling pathways [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. The risk variant reduces Aqp1 promoter activity, expression, and glucose-driven osmotic water transport [3].

In conclusion, Aqp1 plays essential roles in processes like endothelial cell senescence regulation and peritoneal ultrafiltration. Studies using gene knockout models have revealed its functions in these specific areas, which is of great significance for understanding the mechanisms of age-related cardiovascular diseases and peritoneal dialysis-associated complications, providing potential therapeutic targets for these diseases [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/