PT - JOURNAL ARTICLE AU - Sarah White AU - Lauren M. North AU - Emily Haines AU - Lydia M Sullivan AU - Megan Goldberg AU - Jeffrey D. Pressly AU - David S. Weber AU - Frank Park AU - Kevin Regner TI - Gβγ Dimers Modulate Kidney Repair Following Ischemia-Reperfusion Injury in Rats AID - 10.1124/mol.114.092346 DP - 2014 Jan 01 TA - Molecular Pharmacology PG - mol.114.092346 4099 - http://molpharm.aspetjournals.org/content/early/2014/07/21/mol.114.092346.short 4100 - http://molpharm.aspetjournals.org/content/early/2014/07/21/mol.114.092346.full AB - Heterotrimeric G-proteins play a crucial role in the control of renal epithelial cell function during homeostasis and in response to injury. In this report, Gβγ dimer activity was evaluated during the process of renal tubular repair following renal ischemia-reperfusion injury (IRI) in male Sprague Dawley rats. Rats were treated with a small molecule inhibitor of Gβγ activity, gallein (30 or 100 mg/kg), 1 hr after reperfusion and every 24 hours for 3 additional days. Following IRI, renal dysfunction was prolonged following the high-dose gallein treatment in comparison to vehicle treatment during the 7 day recovery period. Renal tubular repair in the outer medulla 7 days after IRI was significantly (P<0.001) attenuated following treatment with high-dose gallein (100 mg/kg) in comparison to low-dose gallein (30 mg/kg), or the vehicle and fluorescein control groups. Gallein treatment significantly reduced (P<0.05) the number of PCNA-positive tubular epithelial cells after 24 hours following the ischemia-reperfusion phase in vivo. In vitro application of gallein on normal rat kidney (NRK-52E) proximal tubule cells significantly reduced (P<0.05) S-phase cell cycle entry compared to vehicle-treated cells as determined by 5'-bromo-2'-deoxyuridine incorporation. Taken together, these data suggest that Gβγ signaling contributes to the maintenance and repair of renal tubular epithelium, and may be a novel therapeutic target for the development of drugs to treat acute kidney injury.