Fluid Retention Caused by Rosiglitazone Is Related to Increases in AQP2 andαENaC Membrane Expression

Abstract

Peroxisome proliferator activated receptor-γ(PPARγ) is a ligand-activated transcription factor of the nuclear hormone receptor superfamily. The decreased phosphorylation of PPARγdue to rosiglitazone (ROS) is the main reason for the increased insulin sensitivity caused by this antidiabetic drug. However, there is no clear evidence whether the nuclear translocation of p-PPARγstimulated by ROS is related to fluid retention. It is also unclear whether the translocation of p-PPARγis associated with the change of aquaporin-2 (AQP2) and epithelial sodium channelαsubunit (αENaC) in membranes, cytoplasm, and nucleus. Our experiments indicate that ROS significantly downregulates nuclear p-PPARγand increases membrane AQP2 andαENaC; however, SR1664 (a nonagonist PPARγligand) reduces p-PPARγand has no effect on AQP2 andαENaC. Therefore, we conclude that in vitro the fluid retention caused by ROS is associated with the increases in membraneαENaC and AQP2 but has little relevance to the phosphorylation of PPARγ.