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Suppression of renal TRPM7 may alleviate kidney injury in the renal transplantation

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Abstract

Purpose

The aim of this study was to investigate the effect of renal cortex transient receptor potential melastatin 7 (TRPM7) suppression on renal ischemia reperfusion injury induced by transplantation in mice.

Methods

M7shRNA was used to decrease the expression of TRPM7 in NRK-52e cells. The mice were subjected to renal intra-parenchymal injection with lentivirus containing M7shRNA to produce hypo-expression of TRPM7 in renal cortex. Cell hypoxia mode and syngeneic renal transplantation in vivo were established. Then the effects of M7shRNA were measured by fluorescent probe for reactive oxygen species (ROS), intracellular calcium and magnesium; Western blot was applied for p38-MAPKs and Bax expression in cell studies. In vivo studies, mice were killed 24 h, 48 h, 72 h, 7 days and 21 days, respectively, after transplantation and the kidneys were dissected. Serum creatinine was measured, and the H&E, Masson’s trichrome staining, TUNEL, Kim-1 and α-smooth muscle actin were used to evaluate pathological change.

Results

In cell model of hypoxia, the level of ROS in NRK-52e-M7shRNA was significantly lower than that in both NRK-52e and NRK-52e control cells, while the activation of p38-MAPKs was limited. In renal transplanted mice, renal function of M7shRNA group was conspicuously better than PBS- and vector-control-treated group. The histological examination showed that renal tubule injury and interstitial fibrosis were lower in M7shRNA-treated group compared with PBS and vector-control group.

Conclusions

Suppression of renal cortex TRPM7 could alleviate kidney injury induced by transplantation in mice. The mechanism may involve reducing the early stage of ischemia reperfusion injury by inhibition of intracellular Ca2+, Mg2+ and ROS.

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Acknowledgments

The authors would like to thank Professor Loren Runnels for his great assistance. The study was supported by grants from the National Natural Science Foundation of China (No.81172734 and No. 81202027) and Fundamental Research Funds for the Central Universities (No. 2012303020211).

Conflict of interests

None.

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Authors and Affiliations

  1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Zhe Meng, Rui Cao, Yongzhi Wang, Tao Liu, Zhonghua Yang & Xinghuan Wang

  2. Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China

    Hong Cao

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  1. Zhe Meng
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  2. Rui Cao
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  3. Yongzhi Wang
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  4. Hong Cao
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  7. Xinghuan Wang
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Correspondence to Xinghuan Wang.

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Meng, Z., Cao, R., Wang, Y. et al. Suppression of renal TRPM7 may alleviate kidney injury in the renal transplantation. World J Urol 32, 1303–1311 (2014). https://doi.org/10.1007/s00345-013-1208-y

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  • DOI: https://doi.org/10.1007/s00345-013-1208-y

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