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

Clin Exp Nephrol. 2022 Jan;26(1):13-21. doi: 10.1007/s10157-021-02129-1. Epub 2021 Aug 31.

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.

Keywords: Fibrosis; Ischemic–reperfusion injury; Renal denervation; miRNA.

MeSH terms

  • Acute Kidney Injury* / genetics
  • Acute Kidney Injury* / metabolism
  • Animals
  • Denervation / methods
  • Fibrosis
  • Humans
  • Kidney
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Rats
  • Reperfusion Injury* / genetics
  • Reperfusion Injury* / prevention & control

Substances

  • MicroRNAs