Abstract
Autophagy is important for cellular survival during renal ischemia/reperfusion (I/R) injury. Ischemic preconditioning (IPC) has a strong renoprotective effect during renal I/R. Our study here aimed to explore the effect of IPC on autophagy during renal I/R injury. Rats were subjected to unilateral renal ischemia with or without prior IPC. Hypoxia/reoxygenation (H/R) injury was induced in HK-2 cells with or without prior hypoxic preconditioning (HPC). Autophagy and apoptosis were detected after reperfusion or reoxygenation for different time. The results showed that the levels of LC3II, Beclin-1, SQSTM1/p62, and cleaved caspase-3 were altered in a time-dependent manner during renal I/R. IPC further induced autophagy as indicated by increased levels of LC3II and Beclin-1, decreased level of SQSTM1/p62, and accumulation of autophagosomes compared to I/R groups at corresponding reperfusion time. In addition, IPC reduced the expression of cleaved caspase-3 and alleviated renal cell injury, as evaluated by the levels of serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) in renal tissues. In conclusion, autophagy and apoptosis are dynamically altered during renal I/R. IPC protects against renal I/R injury and upregulates autophagic flux, thus increasing the possibility for a novel therapy to alleviate I/R-induced acute kidney injury (AKI).
Highlights
Acute kidney injury (AKI) is a common kidney disorder characterized by a rapid loss of renal function resulting in an accumulation of metabolic waste and an imbalance of electrolytes and body fluid [1]
As indicated by the expression of LC3II and Beclin-1 in Figure 2(a), a basal level of autophagy was observed in the sham group, and it increased remarkably between 2 h and 6 h after reperfusion, peaked at 6 h, and began to decline
Autophagy is thought to be influenced by Ischemic preconditioning (IPC) in AKI
Summary
Acute kidney injury (AKI) is a common kidney disorder characterized by a rapid loss of renal function resulting in an accumulation of metabolic waste and an imbalance of electrolytes and body fluid [1]. Renal ischemia/reperfusion (I/R) injury is the most common risk factor for AKI. The tubular segments located within the outer stripe of the outer medulla, including the proximal tubules, are sensitive to hypoxia and I/R injury because of their high rates of adenosine triphosphate consumption. Renal tubular cells activate a myriad of defense mechanisms. Autophagy is induced under various stressful conditions including oxidant injury, cell starvation, growth factor deprivation, and I/R injury [4], and enhanced autophagy has been shown to protect renal tubular epithelial cells from I/R injury in vitro by attenuating apoptosis. Renal proximal tubule-specific autophagy-associated gene (Atg) knockout mice demonstrate autophagy inhibition and I/R injury sensitization compared to their wild-type littermates [5], confirming the renoprotective effect of autophagy in I/Rinduced AKI
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