Abstract
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.
Highlights
Acute kidney injury (AKI) is an abrupt loss of kidney function, which is characterized by increased serum creatinine concentration and decreased urine volume within seven days [1]
We examined the pathophysiological significance of VASH2 expression in I/R-induced AKI using VASH2 knockout mice
In accordance with a previous report [16], compared with WT mice, Vash2 homozygous knockout (Vash2LacZ/LacZ; V2KO) mice did not show any changes in phenotypes, including renal function and morphology (Figure 1)
Summary
Acute kidney injury (AKI) is an abrupt loss of kidney function, which is characterized by increased serum creatinine concentration and decreased urine volume within seven days [1]. Previous studies reported that renal VEGF expression was repressed by I/R injury [11], and administration of VEGF-121 preserved PTC density in post-I/R kidneys [12], suggesting the potential protective effects of VEGF on the PTC network in renal I/R injury. Immunohistochemistry for VASH2 in kidney specimens from patients with CKD revealed increased renal tubular VASH2 staining compared with control specimens [17]. These findings suggest that VASH2 may be upregulated in the kidney in response to a variety of insults and involved in renal pathological processes. Our results suggest that increased renal expression of VASH2 in I/R injury may protect the renal tubular epithelium through protecting PTCs and preventing inflammatory infiltration
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