Kidney Injury Molecule-1 Mediated Autophagy Pathway Participates in Ischemic Preconditioning Evoked Renal Protection

Abstract Background Ischemia-reperfusion injury (IRI) is one of the most vital pathogenesis causing kidney injury, especially during the perioperative periods of partial nephrectomy and renal transplantation, but lacking of effective prevention and treatment strategies. This study was conducted to investigate the influences of ischemic preconditioning (IPC) on the pathological process of mouse bilateral IRI, and to figure out the role of kidney injury molecule-1 (KIM-1) mediated autophagy pathway in this process. Methods Nephron major histocompatibility complex class II (MHC II) conditional knockout (cKO) mice (Six2-Cre+/−; MHC II flox/flox) and the age- and sex-matched littermates from the Six2-Cre−/−; MHC II flox/flox colony (Ctrl) were established to investigate these issues. A 15-minute period of IPC was performed 4 days before the 30-minute of bilateral renal vessel occlusion. Severity of renal IRI in cKO and Ctrl mice with or without IPC were analyzed respectively and correspondingly. Results MHC II cKO mice presented severer kidney injury in both acute and chronic phase of renal IRI. IPC could significantly attenuate ischemia/reperfusion-induced serum creatinine (sCr) and blood urea nitrogen (BUN) increasing, as well as histological KIM-1 expression. However, MHC II cKO mice undergoing IPC showed more deteriorated kidney injury when compared with Ctrl mice, with higher levels of sCr, BUN, KIM-1 expression in the acute phase, and aggravated interstitial fibrosis in the chronic phase. Conclusions IPC could attenuate renal IRI functionally and histologically. KIM-1 mediated autophagy pathway plays a vital role in the IPC induced renal IRI protection.