Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p.
Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p.
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DOI：
10.1038/srep36758
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发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
Hamano K
中科院分区：
文献类型：
--
作者：
Ueno K;Samura M;Nakamura T;Tanaka Y;Takeuchi Y;Kawamura D;Takahashi M;Hosoyama T;Morikage N;Hamano K
缺血预处理（IPC）对器官缺血-灌注损伤具有保护作用。在本研究中，我们研究了通过夹腹主动脉对小鼠下肢进行远程IPC （rIPC）后的相关机制。随后的实验显示脊髓损伤（SCI）后下肢损伤和瘫痪减少。同时，与假手术动物相比，rIPC术后24 h血浆血管内皮生长因子（VEGF）水平升高。在随后的microRNA分析中，rIPC后24小时外泌体中有13个microRNA下调。对股骨cd34阳性骨髓细胞的进一步研究证实，与假手术对照组相比，rIPC后24小时这7种microrna下调。随后基于算法的数据库搜索表明，七个microrna中的两个结合到VEGF mRNA的3 ' UTR上，并且在转染到cd34阳性BM细胞后，anti-miR-762和anti-miR-3072-5p抑制剂导致VEGF浓度升高。目前的数据表明，rIPC通过下调cd34阳性BM细胞中的miR-762和miR-3072-5p，短暂地增加血浆VEGF水平，从而保护器官缺血。
Ischemic preconditioning (IPC) has protective effects against ischemia-perfusion injury of organs. In the present study, we investigated the associated mechanisms after performing remote IPC (rIPC) of lower limbs by clamping abdominal aorta in mice. Subsequent experiments showed decreased damage and paralysis of lower limbs following spinal cord injury (SCI). Concomitantly, plasma vascular endothelial growth factor (VEGF) levels were increased 24 h after rIPC compared with those in sham-operated animals. In subsequent microRNA analyses, thirteen microRNAs were downregulated in exosomes 24 h after rIPC. Further studies of femoral CD34-positive bone marrow (BM) cells confirmed downregulation of these seven microRNAs 24 h after rIPC compared with those in sham-operated controls. Subsequent algorithm-based database searches suggested that two of the seven microRNAs bind to the 3′ UTR of VEGF mRNA, and following transfection into CD34-positive BM cells, anti-miR-762, and anti-miR-3072-5p inhibitors led to increased VEGF concentrations. The present data suggest that rIPC transiently increases plasma VEGF levels by downregulating miR-762 and miR-3072-5p in CD34-positive BM cells, leading to protection against organ ischemia.
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影响因子：
20.1
作者：
Kempf, T;Eden, M;Wollert, KC
通讯作者：
Wollert, KC
DOI：
10.1073/pnas.97.18.10242
发表时间：
2000-08-29
影响因子：
11.1
作者：
Jin, KL;Mao, XO;Greenberg, DA
通讯作者：
Greenberg, DA
影响因子：
3.7
作者：
Ahrens, Ingo;Domeij, Helena;Peter, Karlheinz
通讯作者：
Peter, Karlheinz
影响因子：
37.8
作者：
MURRY, CE;JENNINGS, RB;REIMER, KA
通讯作者：
REIMER, KA
影响因子：
24
作者：
Kamota, Takahiro;Li, Tao-Sheng;Hamano, Kimikazu
通讯作者：
Hamano, Kimikazu