EGFR mediated the renal cell apoptosis in rhabdomyolysis-induced model via upregulation of autophagy

Aims: Rhabdomyolysis is a life-threatening condition. One of the most common complications of rhabdomyolysis is acute kidney injury (AKI), and 10 % of all AKI patients present with rhabdomyolysis. EGFR is associated with different types of AKI. However, the function and regulatory mechanism of EGFR in rhabdomyolysis-induced AKI model remain unknown. Here, we performed the experiments to explore the role of EGFR in this model.Main methods: We used proximal tubule-specific Atg7 knockout mice and Wa-2 mice to establish animal models. Then, the samples were collected for pathology assay and IB detection. In vitro, the BUMPT cells treated with myoglobin were collected for the detection of apoptosis and autophagy. IB detection were processed for the analysis of protein expressions, FCM analysis for the cell apoptosis, GFP-LC3 transfection and immunofluorescent for autophagy.Key findings: EGFR promotes autophagy to mediate rhabdomyolysis-induced AKI via STAT3/Atg7 axis, and gefitinib is a potential therapeutic option for AKI. Here, we demonstrated that EGFR was activated by myoglobin and glycerol both in vitro and in vivo, respectively. Genetic or pharmacological inhibition of EGFR ameliorated myoglobin and glycerol-induced renal cell apoptosis. Mechanistically, EGFR mediated autophagy induction via STAT3/Atg7 axis, thereby resulting in kidney cell apoptosis. Furthermore, Wa-2 mice or gefitinib treatment prevented the progression of rhabdomyolysis-induced AKI as well as renal cell apoptosis and autophagy via inhibiting STAT3/Atg7 axis.Significance: Researchers can use this finding to better study the function and regulatory mechanism of EGFR in RM-induced AKI model. And gefitinib represents a potential target for treatment of AKI.

Automated summary

In this study, it was found that EGFR plays a crucial role in rhabdomyolysis-induced acute kidney injury by promoting autophagy and kidney cell apoptosis via the STAT3/Atg7 axis. Additionally, gefitinib represents a potential therapeutic option for acute kidney injury.