Remote postconditioning ameliorates stroke damage by preventing let-7a and miR-143 up-regulation.
Remote postconditioning ameliorates stroke damage by preventing let-7a and miR-143 up-regulation.
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DOI：
10.7150/thno.48135
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发表时间：
2020
期刊：
影响因子：
12.4
通讯作者：
Pignataro G
中科院分区：
文献类型：
--
作者：
Vinciguerra A;Cepparulo P;Anzilotti S;Cuomo O;Valsecchi V;Amoroso S;Annunziato L;Pignataro G
远程肢体缺血后处理（RLIP）是一种成熟的神经保护策略，能够通过股动脉的亚致死闭塞来保护大脑免受先前有害的缺血性损伤。神经和体液机制已被提议作为将外周信号从肢体传输到大脑所需的介质。此外，不同的研究表明，在大脑水平观察到的保护与一般基因重编程有关，也涉及 microRNA (miRNA) 干预。方法：通过短暂闭塞大脑中动脉（tMCAO）诱导雄性大鼠脑缺血，而 RLIP 则通过 tMCAO 后暂时闭塞同侧股动脉一个周期来实现。在接受 tMCAO 或 RLIP 的大鼠缺血脑样本中评估了 810 个 miRNA 的表达谱。在所有分析的 miRNA 中，有 4 个 miRNA 的表达在中风后上调，并在 RLIP 后恢复到基础水平，因此表明可能参与 RLIP 诱导的神经保护。这些选定的 miRNA 被注入接受远程缺血后处理的大鼠脑室内，并根据脑损伤、神经功能缺损评分和假定靶标的表达来评估其效果。结果：基于微阵列微流控分析，选择了 21 个 miRNA，其表达受到 tMCAO 和 tMCAO 加 RLIP 的显着影响。我们的数据表明：（1）中风诱导let-7a和miR-143上调（2）这两种miRNA参与RLIP诱导的保护作用，（3）HIF1-α有助于其保护作用。事实上，RLIP 后它们的表达减少，并且外源性脑室内输注 let-7a 和 miR-143 模拟物可防止 RLIP 诱导的神经保护和 HIF1-α 过度表达。结论：预防脑缺血引起的大脑let-7a和miR-143过度表达成为中风干预的新的潜在策略。
Remote limb ischemic postconditioning (RLIP) is a well-established neuroprotective strategy able to protect the brain from a previous harmful ischemic insult through a sub-lethal occlusion of the femoral artery. Neural and humoral mechanisms have been proposed as mediators required to transmit the peripheral signal from limb to brain. Moreover, different studies suggest that protection observed at brain level is associated to a general genetic reprogramming involving also microRNAs (miRNAs) intervention. Methods: Brain ischemia was induced in male rats by transient occlusion of the middle cerebral artery (tMCAO), whereas RLIP was achieved by one cycle of temporary occlusion of the ipsilateral femoral artery after tMCAO. The expression profile of 810 miRNAs was evaluated in ischemic brain samples from rats subjected either to tMCAO or to RLIP. Among all analyzed miRNAs, there were four whose expression were upregulated after stroke and returned to basal level after RLIP, thus suggesting a possible involvement in RLIP-induced neuroprotection. These selected miRNAs were intracerebroventricularly infused in rats subjected to remote ischemic postconditioning, and their effect was evaluated in terms of brain damage, neurological deficit scores and expression of putative targets. Results: Twenty-one miRNAs, whose expression was significantly affected by tMCAO and by tMCAO plus RLIP, were selected based on microarray microfluidic profiling. Our data showed that: (1) stroke induced an up-regulation of let-7a and miR-143 (2) these two miRNAs were involved in the protective effects induced by RLIP and (3) HIF1-α contributes to their protective effect. Indeed, their expression was reduced after RLIP and the exogenous intracerebroventricularly infusion of let-7a and miR-143 mimics prevented neuroprotection and HIF1-α overexpression induced by RLIP. Conclusions: Prevention of cerebral let-7a and miR-143 overexpression induced by brain ischemia emerges as new potential strategy in stroke intervention.
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DOI：
10.1038/jcbfm.2008.157
发表时间：
2009-04
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
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Ewing肉瘤肿瘤生长中Let-7，Ras和HIF-1α之间的关联。
影响因子：
--
作者：
Hameiri-Grossman M;Porat-Klein A;Yaniv I;Ash S;Cohen IJ;Kodman Y;Haklai R;Elad-Sfadia G;Kloog Y;Chepurko E;Feinmesser M;Issakov J;Sher O;Luria D;Kollender Y;Weizman A;Avigad S
通讯作者：
Avigad S
影响因子：
9
作者：
通讯作者：
--
影响因子：
8.3
作者：
Lee, Soon-Tae;Chu, Kon;Roh, Jae-Kyu
通讯作者：
Roh, Jae-Kyu
影响因子：
4.7
作者：
Dharap A;Vemuganti R
通讯作者：
Vemuganti R