IKKα Participates In Repair Of Renal Ischemia-Reperfusion Injury

The transcription factor NF-κB has been found critical to the pathogenesis ofrenal ischemia-reperfusion injury, which is a major cause of acute kidney injury(AKI). It has been shown that two separate NF-κB pathways exist, depending on theactivating signal and the cell type, the canonical (depending on IKKβ and NEMO)and the noncanonical pathway (depending solely on IKKα). Several lines ofevidence suggest that IKKα not only is instrumental resolution of inflammation butalso prompts proliferation of tubular epithelial cells. The recovery phase after renalischemia-reperfusion injury is determined by the processes of inflammationregression and tubular epithelial cell proliferation. We hypothesis that IKKα plays agreat role in the repair process of renal ischemia-repefusion reperfusion injury. Widetype male C57BL/6mice were anesthetized with an intraperitoneal injection ofchloral hydrate, they were induced by clamping unilateral (left) kidney pedicle for30min, contralateral (right, untouched) kidney as control. After reperfusion1d,3d,7d,1w,2w, separately, we harvested the kidneys to do further analysis. Mice weretreated before ischemia with IKKαsiRNA or scrambled siRNA, administered byrenal parenchyma. The repair phase of the renal IRI was evaluated by tissuehistopathology, expression of IKKα, P50, tubular epithelial cell proliferate relativecytokines, ki67and CSF-1, anti-inflammation factors IL-10. Tubular epithelial celldamage of experimental group was assessed by a blinded histopathology score ondays0,1,3,7,14(3.78±0.45vs.3.56±0.48vs.3.08±0.35vs.2.01±0.73vs.0.30±0.23;p<0.01), results of western blot showed that IKKα reached peak at3days, andascertained by immunohistochemical staining, furthermore IKKα mainly located in the tubular epithelial cells. In addition, tubular epithelial cell proliferation cytokineski67has the same change, while CSF-1was higher during the repair. In addition,Tregs cells accumulated in the injured renal and was hightest at3days, IL-10wasincreased and remained at higher level, P50increased during the repair of renal IRI.A local injection of IKKα siRNA resulted in inhibition of renal expression ofIKKα,expression of Ki67and IL-10, IKKα blockade reduced the number of Foxp3+T cells in postischemic kidneys during the repair phase. Accordingly IKKαparticipates in the repair process of ischemia reperfusion kidney injury bydiminishing the inflammation and hastening renal tubular epithelial cell proliferation.Though we focused on the phenomenological observations in this study, the detailedmechanism is still to be determined.