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

Abstract

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 γ (PI3Kγ) on inflammatory cells infiltration into the kidney in response to ischemia-reperfusion injury. Compared with wild-type mice, PI3Kγ knockout mice displayed less IRI in the kidney with fewer tubular apoptotic cell. Furthermore, PI3Kγ 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 PI3Kγ inhibitor, displayed less tubular damage, accumulated fewer inflammatory cells, and expressed less proinflammatory molecules in the kidney following IRI. These results demonstrate that PI3Kγ has a critical role in the pathogenesis of kidney damage in IRI, indicating that PI3Kγ inhibition may serve as a potential therapeutic strategy for the prevention of ischemia-reperfusion-induced kidney injury.

Short–Term Preconditioning with Insulin and Glucose Efficiently Protected the Kidney Against Ischemia-Reperfusion Injury via the P-AKT-Bax-Caspase-3 Signaling Pathway in Mice

“…AKT2 was reported involved in glucose metabolism and inhibiting apoptosis. 19 , 28 These three isoforms were not differentiated in this study. The insulin-activated P-AKT may inhibit the apoptosis of tubular epithelial cells through a decrease in the expression of Bax and cleaved caspase-3 in the nucleus.…”

“…Mice were subjected to renal IRI at 9:00 a.m., as previously reported. 19 Briefly, anesthesia was performed by intraperitoneal injections of esketamine (50 mg/kg) and dexmedetomidine (0.25 mg/kg). 20 The kidneys were exposed and subjected to ischemia by clamping renal pedicles with non-traumatic micro-aneurism clamps.…”

Screening Differential Expression Profiles of Urinary microRNAs in a Gentamycin-Induced Acute Kidney Injury Canine Model

“…It was reported that PI3Kγ knockout attenuated kidney injury in an I/R-induced kidney injury mouse model. The PI3Kγ knockout mice had reduced levels of infiltrating neutrophils, macrophages, and T cells in the kidney samples and lowered levels of inflammation [48]. PI3Kγ could also mediate the inflow of macrophages, T cells, and fibroblasts into the kidney, leading to renal fibrosis and injury [49].…”

A short–term pretreatment with insulin and glucose efficiently protected the kidney against Ischemia-Reperfusion injury via the P-AKT-Bax-Caspase-3 signaling pathway in mice

“…The vehicle-treated mice were subcutaneously injected with the same volume of normal saline as the insulin injection. IRI was performed on mice kidneys at 9:00 a.m., as previously reported [17]. Brie y, anesthesia was performed by intraperitoneal injections of esketamine (50 mg/kg) and dexmedetomidine (0.25 mg/kg) [18].…”