rhEPO inhibited cell apoptosis to alleviate acute kidney injury in sepsis by AMPK/SIRT1 activated autophagy.

BACKGROUND

Nowadays, people diagnosed sepsis may develop acute kidney injury (AKI), resulting heavy burden of health care. Recombinant human erythroprotein (rhEPO) has been suggested to have multifunction and may be used in the prevention or treatment of AKI, and its underlying mechanism remains largely unknown.

METHODS

In our study, cell model induced by LPS-activated cell apoptosis in vitro and AKI animal model caused by lipopolysaccharide (LPS) injection in vivo. MTT assay and Flow Cytometry were conducted to analyze cell viability and apoptosis, respectively. Western bot was used to analyze expressions of apoptosis and autophagy associated proteins, and effects on AMPK/SIRT1 pathway.

RESULTS

Our results suggested that rhEPO inhibited LPS-induced cell apoptosis in HK-2 and HEK-293. Moreover, we found that rhEPO activated autophagy to prevented cell apoptosis, changing the expression level of autophagy associated proteins such as LC3-I/LC3-II and P62, and AMPK/SIRT1 pathway was involved in its regulation. Additionally, both EX527 (SIRT1 inhibitor) and Compound C (AMPK inhibitor) blocked the autophagy effects caused by rhEPO and thus reversed the anti-apoptotic effects of rhEPO. Furthermore, our data demonstrated that rhEPO inhibited LPS-induced kidney tubular injury and decreased the expression level of apoptotic proteins by altering the expression level of autophagy related proteins and AMPK/SIRT1 pathway related proteins in vitro.

CONCLUSION

Collectively, rhEPO suppressed LPS-induced cell apoptosis via AMPK/SIRT1 pathway mediated autophagy, and modulating their levels may serve as potential way in preventing AKI.