Influence of renal ischaemia-reperfusion injury on renal neutrophil gelatinase-associated lipocalin receptor (24p3R) in rats

Clin Exp Pharmacol Physiol. 2019 Dec;46(12):1166-1173. doi: 10.1111/1440-1681.13129. Epub 2019 Jul 23.

Abstract

The neutrophil gelatinase-associated lipocalin (NGAL) receptor (24p3R) is expressed in distal nephron and contributes to the endocytosis of NGAL in urine. This study was undertaken to evaluate an influence of renal ischaemia-reperfusion injury on 24p3R. Unilateral renal pedicle was clamped for 0, 10, 20, 30, or 45 minutes in male Wistar rats. Urine was collected for 24 hours after reperfusion, and ischaemic kidney and blood sample were obtained. Apparent histological injury in the ischaemic kidney was detected in the 30 and 45 minutes-treated groups. Urinary NGAL excretion elevated in rats with renal ischaemia for more than 20 minutes, while serum creatinine increased in rats for more than 30 minutes of ischaemia. Renal protein expression of NGAL did not significantly change. Renal mRNA expressions of megalin and cubilin, which are expressed at renal proximal tubules and uptake NGAL, decreased in animals with renal ischaemia for more than 20 minutes. Renal protein expression of 24p3R, which is expressed at renal distal tubules and uptake NGAL, decreased in rats with renal ischaemia for 45 min. This study showed for the first time that renal 24p3R decreased in response to renal ischaemia. As relatively longer renal ischaemia (45 minutes) decreased renal 24p3R protein and increased urinary NGAL excretion, the down-regulation of 24p3R protein might contribute to the elevated urinary excretion of NGAL in rats with unilateral ischaemia-reperfusion injury.

Keywords: 24p3R; ischaemia-reperfusion; kidney injury; megalin; neutrophil gelatinase-associated lipocalin.

MeSH terms

  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Biomarkers / metabolism
  • Cells, Cultured
  • Gene Expression Regulation
  • Kidney / metabolism*
  • Kidney Tubules, Proximal / metabolism
  • Lipocalin-2 / metabolism
  • Lipocalin-2 / urine
  • Male
  • Nephrons / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism*
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology

Substances

  • 24p3R receptor, rat
  • Biomarkers
  • Lcn2 protein, rat
  • Lipocalin-2
  • Receptors, Cell Surface