Dingwei Yang

Oxidative stress and inflammation response have been found to be associated with renal ischemia reperfusion (I/R) injury through an undefined mechanism. The aim of our study is to explore the influence of Wnt/β-catenin signaling pathway on oxidative stress and inflammation response during renal I/R injury. The results of our study demonstrated that oxidative stress was induced whereas antioxidative factors were suppressed by renal I/R injury. Besides, the transcriptions and activities of pro-inflammation factors were also upregulated by renal I/R injury. Interestingly, inhibition of Wnt/β-catenin signaling pathway significantly attenuated I/R-mediated oxidative stress and inflammation response. Therefore, our results report a novel pathway responsible for renal I/R injury. Inhibition of Wnt/β-catenin signaling pathway would be considered as an effective approach to regulate oxidative stress and inflammation response in reperfused kidney.

Context: Cell death and inflammation response have been found to the primary features of acute kidney injury. Objective: The aim of our study is to figure out the molecular mechanism by which hypoxia-reoxygenation injury affects the viability of tubular cell death. Materials and methods: HK2 cells were treated with hypoxia-reoxygenation injury in vitro. Pathway agonist was added into the medium of HK2 cell to activate MAPK-EEK-CREB axis. Results: Hypoxia-reoxygenation injury reduced HK2 cell viability and increased cell apoptosis rate in vitro. Besides, inflammation response has been found to be induced by hypoxia-reoxygenation injury in HK2 cells in vitro. In addition, MAPK-ERK-CREB pathway was deactivated during hypoxia-reoxygenation injury. Interestingly, activation of MAPK-ERK-CREB pathway could attenuate hypoxia-reoxygenation injury-mediated HK2 cell apoptosis and inflammation. Mechanistically, MAPK-ERK-CREB pathway activation upregulated the transcription of anti-apoptotic genes and reduced the levels of pro-apoptotic factors under hypoxia-reoxygenation injury. Conclusions: Our results report a novel signaling pathway responsible for acute kidney injury-related tubular cell death. Activation of MAPK-ERK-CREB signaling could protect tubular cell against hypoxia-reoxygenation-related cell apoptosis and inflammation response.