Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury
Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury
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DOI：
10.3390/ijms21124545
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Wada, Jun
中科院分区：
文献类型：
--
作者：
Miyake, Hiromasa;Tanabe, Katsuyuki;Wada, Jun
急性肾损伤（阿基）已越来越多地被认为是转变为慢性肾脏疾病的风险因素。最近的证据表明，肾小管周围毛细血管的内皮损伤可以加速肾损伤的进展。Vasohibin-2（VASH 2）是一种新的促血管生成因子，可促进肿瘤血管生成。然而，VASH 2在肾脏疾病中的病理生理作用仍然未知。在本研究中，我们研究了VASH 2缺陷对缺血再灌注（I/R）损伤诱导的阿基进展的影响。在雄性野生型（WT）和Vash 2纯合基因敲除小鼠中，通过双侧夹闭肾蒂25分钟诱导I/R损伤。24小时后，I/R损伤诱导的肾功能不全和肾小管损伤在VASH 2缺陷小鼠中比WT小鼠更严重，具有更显著的中性粒细胞浸润和肾小管周围毛细血管损失。诱导I/R损伤后，VASH 2在受损肾小管中的表达显著增加。这些结果表明，肾小管上皮细胞中VASH 2的表达可能是必要的，以减轻I/R损伤诱导的阿基，可能通过保护管周毛细血管和防止炎症浸润。
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) andVash2homozygous 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.