Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model
Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model
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DOI：
10.1152/ajprenal.00045.2019
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发表时间：
2019-08-01
影响因子：
4.2
通讯作者：
Wada, Jun
中科院分区：
文献类型：
--
作者：
Tanimura, Satoshi;Tanabe, Katsuyuki;Wada, Jun
急性肾损伤（阿基）是临床上常见的疾病。特别是继发于心血管手术和给予肾毒性剂，并且越来越多地被认为是引发向慢性肾病转变的原因。阐明阿基的发病机制可以促进新的预防策略的发展，因为医院获得性阿基的发生通常是可以预期的。Vasohibin-1（VASH 1）最初被鉴定为来源于内皮细胞的抗血管生成因子。随后报道了内皮细胞中的VASH 1表达增强细胞应激耐受性。考虑到维持肾小管周围毛细血管在预防MU进展中的重要性，本研究旨在研究VASH 1缺失是否参与顺铂诱导的MU的发病机制。为此，我们向雄性C57 BL/6 J野生型（WT）和VASH 1杂合敲除（VASH 1（+/-））小鼠腹膜内注射20 mg/kg顺铂或溶媒溶液。顺铂注射后72小时，VASH 1（+/-）小鼠中血清肌酐浓度升高和肾小管损伤伴细胞凋亡和氧化应激比WT小鼠更明显。VASH 1缺乏也加速了顺铂诱导的肾小管周围毛细血管损失。此外，顺铂处理的VASH 1（+/-）小鼠肾小管周围毛细血管中ICAM-1表达增加与巨噬细胞更明显地浸润到肾脏中相关。综上所述，VASH 1表达可能通过维持肾小管周围毛细血管的数量和功能对顺铂诱导的阿基具有保护作用。
Acute kidney injury (AKI) is frequently encountered in clinical practice. particularly secondarily to cardiovascular surgery and administration of nephrotoxic agents, and is increasingly recognized for initiating a transition to chronic kidney disease. Clarifying the pathogenesis of AKI could facilitate the development of novel preventive strategies, because the occurrence of hospital-acquired AKI is often anticipated. Vasohibin-1 (VASH1) was initially identified as an antiangiogenic factor derived from endothelial cells. VASH1 expression in endothelial cells has subsequently been reported to enhance cellular stress tolerance. Considering the importance of maintaining peritubular capillaries in preventing the progression of MU, the present study aimed to examine whether VASH1 deletion is involved in the pathogenesis of cisplatin-induced MU. For this, we injected male C57BL/6J wild-type (WT) and VASH1 heterozygous knockout (VASH1(+/-)) mice intraperitoneally with either 20 mg/kg cisplatin or vehicle solution. Seventy-two hours after cisplatin injection, increased serum creatinine concentrations and renal tubular injury accompanied by apoptosis and oxidative stress were more prominent in VASH1(+/-) mice than in WT mice. Cisplatin-induced peritubular capillary loss was also accelerated by VASH1 deficiency. Moreover, the increased expression of ICAM-1 in the peritubular capillaries of cisplatin-treated VASH1(+/-) mice was associated with a more marked infiltration of macrophages into the kidney. Taken together, VASH1 expression could have protective effects on cisplatin-induced AKI probably by maintaining the number and function of peritubular capillaries.