TY - JOUR
T1 - Genetic deletion of vasohibin-2 exacerbates ischemia-reperfusion-induced acute kidney injury
AU - Miyake, Hiromasa
AU - Tanabe, Katsuyuki
AU - Tanimura, Satoshi
AU - Nakashima, Yuri
AU - Morioka, Tomoyo
AU - Masuda, Kana
AU - Sugiyama, Hitoshi
AU - Sato, Yasufumi
AU - Wada, Jun
N1 - Funding Information:
Funding: This research was funded by JSPS KAKENHI, grant number JP15K09263 (2015–2017 to K.T) and JP18K08210 (2018–2020 to K.T.), and the Cooperative Research Project Program of Joint Usage/Research Center at the Institute of Development, Aging and Cancer, Tohoku University (2017–2018 to K.T).
Funding Information:
This research was funded by JSPS KAKENHI, grant number JP15K09263 (2015?2017 to K.T) and JP18K08210 (2018?2020 to K.T.), and the Cooperative Research Project Program of Joint Usage/Research Center at the Institute of Development, Aging and Cancer, Tohoku University (2017?2018 to K.T).
Publisher Copyright:
© MDPI AG. All rights reserved.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
KW - Acute kidney injury
KW - Ischemia-reperfusion
KW - Oxidative stress
KW - Peritubular capillaries
KW - Vasohibin-2
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U2 - 10.3390/ijms21124545
DO - 10.3390/ijms21124545
M3 - Article
C2 - 32604722
AN - SCOPUS:85087411003
VL - 21
SP - 1
EP - 14
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 12
M1 - 4545
ER -