Ccl2 deficiency protects against chronic renal injury in murine renovascular hypertension.
Ccl2 deficiency protects against chronic renal injury in murine renovascular hypertension.
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DOI：
10.1038/s41598-018-26870-y
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发表时间：
2018-06-05
影响因子：
4.6
通讯作者：
Grande JP
中科院分区：
文献类型：
--
作者：
Kashyap S;Osman M;Ferguson CM;Nath MC;Roy B;Lien KR;Nath KA;Garovic VD;Lerman LO;Grande JP
炎症在肾血管性高血压（RVH）的肾脏和心血管疾病的发病机制中起重要作用。Ccl 2是炎症的重要介质，并且在手术后24小时内诱导以在鼠2肾1夹模型中建立RVH，这是间质性炎症、纤维化或肾小管萎缩发作之前的时间。我们检验了Ccl 2缺乏保护肾动脉狭窄（RAS）所致肾血管性高血压小鼠的狭窄肾（STK）免于慢性肾损伤的假设。对野生型（WT）和Ccl 2敲除（KO）小鼠进行RAS手术;对动物进行四周研究。在患有RVH的WT和Ccl 2 KO小鼠中，肾血流量降低至相似程度。如通过磁共振成像（MRI）评估的，在Ccl 2 KO小鼠中狭窄肾的灌注显著减少。手术后，WT中的狭窄肾体积显著减小，但Ccl 2 KO小鼠中没有。通过血氧水平依赖性MRI（BOLD-MRI）评估，在Ccl 2 KO小鼠的狭窄肾脏中观察到皮质缺氧。Ccl 2 KO小鼠显示皮质萎缩比WT RAS小鼠少。Ccl 2缺陷减少了浸润的单个核细胞的数量和Ccl 5、Ccl 7、Ccl 8、Ccr 2和Cd 206的表达。我们得出结论，CCl 2是RVH慢性肾损伤的关键介质。
Inflammation plays an important role in the pathogenesis of renal and cardiovascular disease in renovascular hypertension (RVH). Ccl2 is an important mediator of inflammation, and is induced within 24 hours following surgery to establish RVH in the murine 2 kidney 1 clip model, a time prior to onset of interstitial inflammation, fibrosis, or tubular atrophy. We tested the hypothesis that Ccl2 deficiency protects the stenotic kidney (STK) from development of chronic renal damage in mice with renovascular hypertension due to renal artery stenosis (RAS). RAS surgery was performed on wild type (WT) and Ccl2 knock out (KO) mice; animals were studied for four weeks. Renal blood flow was reduced to similar extent in both WT and Ccl2 KO mice with RVH. Perfusion of the stenotic kidney was significantly reduced in Ccl2 KO mice as assessed by magnetic resonance imaging (MRI). Stenotic kidney volume in WT, but not in Ccl2 KO mice, was significantly reduced following surgery. Cortical hypoxia was observed in the stenotic kidney of Ccl2 KO mice, as assessed by blood oxygen level-dependent MRI (BOLD-MRI). Ccl2 KO mice showed less cortical atrophy than WT RAS mice. Ccl2 deficiency reduced the number of infiltrating mononuclear cells and expression of Ccl5, Ccl7, Ccl8, Ccr2 and Cd206. We conclude that Ccl2 is a critical mediator of chronic renal injury in RVH.
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影响因子：
7.5
作者：
Fukuda, Daiju;Enomoto, Soichiro;Sata, Masataka
通讯作者：
Sata, Masataka
G0/G1开关2的抑制可改善慢性肾脏疾病的肾脏炎症。
影响因子：
11.1
作者：
Matsunaga N;Ikeda E;Kakimoto K;Watanabe M;Shindo N;Tsuruta A;Ikeyama H;Hamamura K;Higashi K;Yamashita T;Kondo H;Yoshida Y;Matsuda M;Ogino T;Tokushige K;Itcho K;Furuichi Y;Nakao T;Yasuda K;Doi A;Amamoto T;Aramaki H;Tsuda M;Inoue K;Ojida A;Koyanagi S;Ohdo S
通讯作者：
Ohdo S
影响因子：
6
作者：
Nath, KA;Kanakiriya, SKR;Katusic, ZS
通讯作者：
Katusic, ZS
影响因子：
6
作者：
Kitagawa, K;Wada, T;Yokoyama, H
通讯作者：
Yokoyama, H
影响因子：
3.8
作者：
Panee, Jun
通讯作者：
Panee, Jun