Hyeogsun Kwon, David R Hall, Houda O Maaroufi, Ryan C Smith
Prostaglandin E2 (PGE2) is a bioactive lipid mediator with essential roles in insect physiology, immunity, and reproduction. However, PGE2 function in mosquitoes remains poorly understood, particularly given that mosquito physiology is uniquely shaped by the metabolic and osmotic demands of blood feeding. Herein, we investigate the temporal expression of the PGE2 receptor (PGE2R) in the Malpighian tubules and hindgut of Anopheles gambiae, examining its role in fluid excretion and uric acid metabolism after PGE2 administration and blood feeding. PGE2R expression is upregulated at 24 h and 48 h post-blood feeding in Malpighian tubules and the hindgut, suggesting potential roles in metabolic waste detoxification. PGE2 treatment induced fluid excretion and enhanced hindgut contraction frequency in naïve mosquitoes. Immunolocalization experiments reveal that PGE2R is localized to principal cell nuclei in the Malpighian tubules following blood feeding, suggesting that PGE2 signaling may modulate transcriptional expression associated with nitrogenous waste metabolism. Additional experiments demonstrate that PGE2 signaling influences urate oxidase expression in mosquito tissues, most notably the Malpighian tubules, leading to uric acid accumulation as a potential antioxidant defense mechanism or to prevent further oxidative stress after blood ingestion. Collectively, our findings uncover a previously unrecognized role of PGE2 signaling in regulating osmotic balance and metabolic homeostasis in mosquitoes following blood feeding.