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Renal denervation alleviates renal ischemic reperfusion injury-induced acute and chronic kidney injury in rats partly by modulating miRNAs

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Abstract

Background

Renal denervation (RDN) has been used to promote kidney injury repair, whereas miRNAs have been found to be involved in the pathophysiology of renal injury. However, the miRNA alterations that occur after RDN and the related protective mechanisms remain to be determined.

Methods

Renal ischemic reperfusion injury (IRI) rat model was established and RDN was performed. Animals were killed at 24 h and 2 weeks following the operation. Tyrosine hydroxylase (TH) levels, renal function, tubular cell apoptosis and histological sections were examined at 24 h, whereas renal fibrosis and capillary vessels were assessed at 2 weeks. Furthermore, the expression of miRNAs in the injured kidney was determined using micro-array and the target genes were analyzed.

Results

We found that TH was eliminated and that renal function was improved in the denervation group at 24 h. RDN reduced tubular cell apoptosis and mitigated the histological lesion. Furthermore, an increase of capillary vessel density and reduction of renal fibrosis were observed after 2 weeks. Moreover, the numbers of miRNAs were up-regulated after RDN treatment, and the miRNAs targeted pro-angiogenic, anti-fibrotic and inflammatory pathways.

Conclusions

RDN is a reliable method for alleviating IRI-induced acute and chronic kidney injury, and modulating the miRNA-related pro-angiogenic, anti-fibrotic or inflammatory pathways involved in this process.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study is supported by grants from the National Natural Science Foundation of China (No.81900618; 81871149; 8601267) and the Shanghai Sailing Program (18YF1415000).

Author information

Author notes

  1. Xiangyu Zou, Sihao Lin and Liang Zhong are Co-first authors.

Authors and Affiliations

  1. Department of Urology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Dongfang road, 1678, Shanghai, 200127, China

    Xiangyu Zou, Liang Zhong & Jie Sun

  2. Department of Urology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai, 201803, China

    Sihao Lin & Yingjian Zhu

  3. Department of Neurology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Dongfang road, 1678, Shanghai, 200127, China

    Jie Liu

  4. Department of Nephrology, The First Hospital Affiliated to Jinan University, Guangzhou, 510630, China

    Yu Meng

Authors
  1. Xiangyu Zou
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  2. Sihao Lin
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  3. Liang Zhong
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  4. Jie Liu
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Corresponding authors

Correspondence to Yu Meng, Yingjian Zhu or Jie Sun.

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Ethical approval

In this study, all works involving animals were in accordance with the animal use protocol enacted by the Institutional Animal Care and Use committees of School of Medicine, Shanghai Jiao Tong University (SCMCIACUC-K2019042).

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Zou, X., Lin, S., Zhong, L. et al. Renal denervation alleviates renal ischemic reperfusion injury-induced acute and chronic kidney injury in rats partly by modulating miRNAs. Clin Exp Nephrol 26, 13–21 (2022). https://doi.org/10.1007/s10157-021-02129-1

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  • DOI: https://doi.org/10.1007/s10157-021-02129-1

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