Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury

Int J Mol Sci. 2020 Jun 26;21(12):4545. doi: 10.3390/ijms21124545.


Acute kidney injury (AKI) has been increasingly recognized as a risk factor for transition to chronic kidney disease. Recent evidence suggests that endothelial damage in peritubular capillaries can accelerate the progression of renal injury. Vasohibin-2 (VASH2) is a novel proangiogenic factor that promotes tumor angiogenesis. However, the pathophysiological roles of VASH2 in kidney diseases remain unknown. In the present study, we examined the effects of VASH2 deficiency on the progression of ischemia-reperfusion (I/R) injury-induced AKI. I/R injury was induced by bilaterally clamping renal pedicles for 25 min in male wild-type (WT) and Vash2 homozygous knockout mice. Twenty-four hours later, I/R injury-induced renal dysfunction and tubular damage were more severe in VASH2-deficient mice than in WT mice, with more prominent neutrophil infiltration and peritubular capillary loss. After induction of I/R injury, VASH2 expression was markedly increased in injured renal tubules. These results suggest that VASH2 expression in renal tubular epithelial cells might be essential for alleviating I/R injury-induced AKI, probably through protecting peritubular capillaries and preventing inflammatory infiltration.

Keywords: acute kidney injury; ischemia-reperfusion; oxidative stress; peritubular capillaries; vasohibin-2.

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Angiogenic Proteins
  • Animals
  • Apoptosis*
  • Kidney Tubules / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidative Stress
  • Reperfusion Injury / complications*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology


  • Angiogenic Proteins
  • VASH2 protein, mouse