CaMKII may regulate renal tubular epithelial cell apoptosis through YAP/NFAT2 in acute kidney injury mice

Abstract

Aim

Renal tubular epithelial cell (RTEC) apoptosis is important in acute kidney injury (AKI). Calcium/calmodulin-dependent protein kinase II (CaMKII) plays an important role in cell apoptosis, but its potential role in AKI remains unknown.

Methods

Using co-immunoprecipitation, immunofluorescence, immunohistochemistry, western blotting, flow cytometry, and cell transfection, this study aimed to verify whether CaMKII is involved in RTEC apoptosis and to explore the underlying mechanism.

Results

We found that CaMKII was involved in RTEC apoptosis. In adriamycin-induced AKI mice, serum creatinine levels, cell apoptosis, CaMKII activity, and nuclear factor of activated T cells 2 (NFAT2) levels increased, whereas nuclear Yes-associated protein (YAP) expression decreased; inhibition of CaMKII activity reversed these changes. Phosphorylated CaMKII could bind to phosphorylated YAP in the cytoplasm and block it from entering the nucleus, thereby failing to inhibit NFAT2-mediated cell apoptosis. Sequestrated phosphorylated YAP in the RTEC cytoplasm was finally degraded by ubiquitination.

Conclusion

CaMKII may regulate RTEC apoptosis through YAP/NFAT2 in AKI mice. CaMKII may be a potent molecular target for AKI treatment.

Keywords:

• Calcium/calmodulin-dependent protein kinase II
• yes-associated protein
• nuclear factor of activated T cells
• cell apoptosis
• acute kidney injury

Author contributions

Zongshun Huang contributed to the study conception and design, and acquired funding. Yonghua Peng, Guibao Ke, Yun Xiao, and Yaqi Chen performed the experiments. Zongshun Huang wrote and edited the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81700594), the Natural Science Foundation of Guangdong Province, China (2017A030310075), and the Basic and Applied Basic Research Project of program of the Guangzhou Science and Technology Plan (202201020403).