Abstract
Nephrolithiasis is a common urological disease accompanied by high morbidity worldwide. Evidences indicate that high-level CaOx crystals in the body can lead to renal tubular epithelial cell (RTEC) injury and RTEC injury is a critical precipitating factor for the formation of kidney stones. FGF21 has recently been revealed as the considerable marker in various kidney dysfunction and exerts the nephroprotective effects in various kidney diseases. This current study was formulated to fully elucidate the biological role of FGF21 in nephrolithiasis and probe into the intrinsic mechanisms underlying the protective effects of FGF21 against RTEC injury. In this work, HK-2 cells were incubated with 100 mg/ml COM for 24 h to establish in vitro RTEC injury model. COM-treated HK-2 cells were transfected with Oe-FGF21 to perform gain-of-function experiments. For rescue experiments, HK-2 cells were pretreated with 10 μM Nrf2 inhibitor ML385 for 24 h to thoroughly discuss the role of Nrf2 signaling in FGF21-mediating nephroprotective effects. It was verified that overexpression of FGF21 relieved COM-induced proliferation inhibition, cell injury, apoptosis, oxidative damage and ferroptosis of RTECs. ML385 treatment partially abolished the protective effects of FGF21 against COM injury in RTECs. In conclusion, up-regulation of FGF21 can relieve COM-induced proliferation inhibition, cell injury, apoptosis, oxidative damage and ferroptosis of RTECs through activating Nrf2 signaling pathway.
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The datasets analyzed during the current study are available from the corresponding author on reasonable request.
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This research was funded by Hangzhou Medical Health Science and Technology Project (B20200515) and Hangzhou Biomedicine and Health Industry Development Support Science and Technology Project (2023WJC001).
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Jie Zhang, Guanding Zhang and Chao Chen contributed to the concept and designed the study. Jie Zhang, Guanding Zhang, Lijun Jiang, Danyang Qiu and Guoping Wang performed the experiments. Jie Zhang and Guanding Zhang contributed to the data collection and analysis. Jie Zhang, Guanding Zhang and Chao Chen wrote the manuscript. Chao Chen critically revised the manuscript. All authors read and approved the final manuscript and can confirm the authenticity of all the raw data.
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Zhang, J., Zhang, G., Jiang, L. et al. FGF21 relieves calcium oxalate-induced cell injury, apoptosis, oxidative damage and ferroptosis of renal tubular epithelial cells through activating Nrf2 signaling pathway. Cytotechnology (2024). https://doi.org/10.1007/s10616-024-00633-2
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DOI: https://doi.org/10.1007/s10616-024-00633-2