Effect of mesenchymal stem cells on ferroptosis in cisplatin-induced acute kidney injury of mice

doi:10.3877/cma.j.issn.2095-3216.2023.04.002

Abstract

Abstract:

Objective

To investigate the effect of mesenchymal stem cells (MSCs) on ferroptosis in cisplatin-induced acute kidney injury (AKI) of mice.

Methods

Eighteen 8-week-old male C57BL/6 mice were randomly divided into a model group, an MSCs treatment group, and a control group with 6 mice each. The AKI model was induced by a single intraperitoneal injection of 20 mg/kg cisplatin. After 24 h of the cisplatin-induction, the treatment group was given a single intraperitoneal injection of 1×10⁶ MSCs. The mice were sacrificed on day 3 with the kidneys and blood being collected. An in vivo fluorescence imaging system was used to observe the distribution and survival of MSCs in the mice. Serum creatinine (Scr) and blood urea nitrogen (BUN) were detected. Renal tissue was stained with PAS, and mitochondrial morphology of renal cells was observed by transmission electron microscope. The levels of malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) in kidney tissues were detected to evaluate the ferroptosis. The protein expression of glutathione peroxidase 4 (GPX4) and nuclear factor E2-related factor 2 (Nrf2) was detected by Western blotting.

Results

The results of in vivo imaging system showed that MSCs transplanted were colonized in the abdominal cavity and played the role. The model group showed higher levels than the control group, while the treatment group showed lower levels than the model group, in Scr and BUN as well as the acute tubular necrosis scores (P<0.01). Compared with the control group, the model group had higher level of MDA, but lower levels of GSH and SOD (P<0.01). Compared with the model group, the treatment group had lower level of MDA (P<0.01), but higher levels of GSH (P<0.01) and SOD (P<0.05). Compared with the control group, the model group showed the characteristics of cell ferroptosis such as mitochondrial atrophy, membrane density increase, and reduced mitochondrial crista, which were alleviated in the treatment group. Compared with the control group, the expression of GPX4 and Nrf2 proteins in the model group was significantly down-regulated (P<0.01), but was up-regulated in the treatment group (P<0.05).

Conclusion

MSCs could alleviate the cisplatin-induced injury in the renal tubules of mice by inhibiting the cellular ferroptosis.

Key words: Acute kidney injury, Mesenchymal stem cells, Ferroptosis

Yanqi Song, Xuejing Ren, Wenjuan Wang, Qiuxia Han, Yue Xu, Kaiting Zhuang, Tuo Xiao, Guangyan Cai. Effect of mesenchymal stem cells on ferroptosis in cisplatin-induced acute kidney injury of mice[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(04): 187-193.

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Figures/Tables 5

References 18

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