Renal tubular cell death and inflammation response are regulated by the MAPK-ERK-CREB signaling pathway under hypoxia-reoxygenation injury.

Cell death and inflammation response have been found to the primary features of acute kidney injury. The aim of our study is to figure out the molecular mechanism by which hypoxia-reoxygenation injury affects the viability of tubular cell death. HK2 cells were treated with hypoxia-reoxygenation injury . Pathway agonist was added into the medium of HK2 cell to activate MAPK-EEK-CREB axis. Hypoxia-reoxygenation injury reduced HK2 cell viability and increased cell apoptosis rate . Besides, inflammation response has been found to be induced by hypoxia-reoxygenation injury in HK2 cells . 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. 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.