Recent data from animal experiments and clinical trials indicate that ischemic preconditioning (IPC) confers protection from renal ischemia-reperfusion (I/R) injury. Nevertheless, the underlying mechanisms for this protective effect remain elusive. Emerging evidence shows that autophagy is associated with the protective effect of IPC. The aim of this study was to investigate the role of autophagy in IPC-induced protection against renal I/R injury, as well as the mechanisms underlying heme oxygenase-1 (HO-1)-regulated autophagy.

IPC was produced by 5 minutes of ischemia followed by 10 minutes of reperfusion prior to 30 minutes of ischemia. In a mouse model of renal I/R injury, mice were pretreated with bafilomycin A1 (0.3 mg/kg) or rapamycin (0.25 mg/kg) for 30 min prior to ischemia to evaluate the contribution of autophagy to the protective effects of IPC. To determine whether HO-1 is required for IPC-mediated autophagy and renal protection against I/R injury, we employed a HO-1 inhibitor Tin Protoporphyrin IX (SnPP, 50 mg/kg) to treat mice 30 min prior to ischemia.

IPC ameliorated renal ischemia/reperfusion injury, as indicated by lower serum creatinine (CREA) and blood urea nitrogen (BUN) levels, less induction of proinflammatory cytokines, and less severe ischemia/reperfusion-associated histopathologic changes. IPC induced autophagy activation, as indicated by an increase of LC3-II, degradation of p62, and accumulation of autophagic vacuoles in response to I/R injury. When IPC–induced autophagy was inhibited with bafilomycin A1 in mice, renal I/R injury was worsened, whereas rapamycin treatment increased autophagy and mimicked the protective effects of IPC. Furthermore, IPC increased HO-1 expression. The inhibition of HO-1 with SnPP in mice decreased IPC–induced autophagy and diminished the protective effects of IPC against ischemia/reperfusion injury.

Collectively, these findings indicate that IPC attenuate renal I/R injury, and the protective mechanism appeared to involve its ability to induce autophagy via HO-1.

CITATION INFORMATION: Hwang J., Choi H., Kim M., Jun K., Kown K., Park S., Kim J., Moon I. Ischemic Preconditioning Ameliorates Renal Ischemia-Reperfusion Injury in Mice via Heme Oxygenase-1-Mediated Autophagy Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress