Phosphoinositide 3 Kinase γ Plays a Critical Role in Acute Kidney Injury

Inflammatory cells contribute to the pathogenesis of renal ischemia-reperfusion injury (IRI). However, the signaling mechanisms underlying the infiltration of inflammatory cells into the kidney are not well understood. In this study, we examined the effects of phosphoinositide 3 kinase gamma (PI3K gamma) on inflammatory cells infiltration into the kidney in response to ischemia-reperfusion injury. Compared with wild-type mice, PI3K gamma knockout mice displayed less IRI in the kidney with fewer tubular apoptotic cell. Furthermore, PI3K gamma deficiency decreased the number of infiltrated neutrophils, macrophages, and T cells in the kidney, which was accompanied by a decrease in the expression of pro-inflammatory cytokines in the kidney. Moreover, wild-type mice treated with AS-605240, a selective PI3K gamma inhibitor, displayed less tubular damage, accumulated fewer inflammatory cells, and expressed less proinflammatory molecules in the kidney following IRI. These results demonstrate that PI3K gamma has a critical role in the pathogenesis of kidney damage in IRI, indicating that PI3K gamma inhibition may serve as a potential therapeutic strategy for the prevention of ischemia-reperfusion-induced kidney injury.

Automated summary

This study suggests that phosphoinositide 3 kinase gamma (PI3K gamma) plays a critical role in the infiltration of inflammatory cells into the kidney during renal ischemia-reperfusion injury (IRI). Inhibition or deficiency of PI3K gamma can reduce kidney damage, decrease inflammatory cell infiltration, and decrease the expression of pro-inflammatory molecules. These findings indicate that targeting PI3K gamma may be a potential therapeutic strategy for preventing IRI-induced kidney injury.