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

Abstract

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.

Keywords:

• Renal hypoxia-reoxygenation injury
• MAPK-ERK-CREB pathway
• apoptosis
• inflammation

Disclosure statement

No potential conflict of interest was reported by the authors.