miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models.
miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models.
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miR-1 加剧小鼠模型中的心脏缺血再灌注损伤
DOI：
10.1371/journal.pone.0050515
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Pan Z;Sun X;Ren J;Li X;Gao X;Lu C;Zhang Y;Sun H;Wang Y;Wang H;Wang J;Xie L;Lu Y;Yang B
最近的研究揭示了microRNAs(MiRNAs)在调节心脏损伤中的关键作用。其中，心脏富集型microRNA-1(miR-1)已被广泛研究并被证明对心肌细胞有害。然而，关于miR-1在心脏损伤中的作用的体内确凿证据仍然缺乏，系统下调miR-1表达的潜在治疗优势仍未被探索。本研究采用miR-1转基因小鼠(miR-1TG)和锁定核酸修饰的抗miR-1寡核苷酸(LNA-anttimiR-1)，探讨miR-1对心肌缺血再灌注损伤(缺血30min再灌注24 h)的影响。MiR-1Tg组小鼠心脏miR-1水平显著升高，而LNA-anttimiR-1处理组小鼠心脏miR-1水平受到抑制。缺血再灌注损伤时，miR-1过表达加重心肌损伤，表现为LDH、CK水平、caspase-3表达、细胞凋亡和心肌梗死面积增加。相反，LNA-AntimiR-1治疗可显著减轻心肌缺血/再灌注损伤。MIR-1显著抑制PKC、ε和HSP60的表达，并被MIR-1抑制，这可能是MIR-1在心脏损伤中作用的分子机制之一。此外，荧光素酶检测证实miR-1对蛋白激酶C受体ε和热休克蛋白60具有直接调节作用。综上所述，本研究表明miR-1是心脏损伤的原因之一，全身应用LNA-anttimiR-1治疗可以有效地改善这一问题。
Recent studies have revealed the critical role of microRNAs (miRNAs) in regulating cardiac injury. Among them, the cardiac enriched microRNA-1(miR-1) has been extensively investigated and proven to be detrimental to cardiac myocytes. However, solid in vivo evidence for the role of miR-1 in cardiac injury is still missing and the potential therapeutic advantages of systemic knockdown of miR-1 expression remained unexplored. In this study, miR-1 transgenic (miR-1 Tg) mice and locked nucleic acid modified oligonucleotide against miR-1 (LNA-antimiR-1) were used to explore the effects of miR-1 on cardiac ischemia/reperfusion injury (30 min ischemia followed by 24 h reperfusion). The cardiac miR-1 level was significantly increased in miR-1 Tg mice, and suppressed in LNA-antimiR-1 treated mice. When subjected to ischemia/reperfusion injury, miR-1 overexpression exacerbated cardiac injury, manifested by increased LDH, CK levels, caspase-3 expression, apoptosis and cardiac infarct area. On the contrary, LNA-antimiR-1 treatment significantly attenuated cardiac ischemia/reperfusion injury. The expression of PKCε and HSP60 was significantly repressed by miR-1 and enhanced by miR-1 knockdown, which may be a molecular mechanism for the role miR-1 in cardiac injury. Moreover, luciferase assay confirmed the direct regulation of miR-1 on protein kinase C epsilon (PKCε) and heat shock protein 60 (HSP60). In summary, this study demonstrated that miR-1 is a causal factor for cardiac injury and systemic LNA-antimiR-1 therapy is effective in ameliorating the problem.
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microRNA和心血管疾病。
DOI：
10.1111/j.1742-4658.2011.08090.x
发表时间：
2011-05
期刊：
The FEBS journal
影响因子：
--
作者：
Ono K;Kuwabara Y;Han J
通讯作者：
Han J
DOI：
10.1083/jcb.200306132
发表时间：
2003-11-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kaufman BA;Kolesar JE;Perlman PS;Butow RA
通讯作者：
Butow RA
影响因子：
82.9
作者：
Yang, Baofeng;Lin, Huixian;Wang, Zhiguo
通讯作者：
Wang, Zhiguo
影响因子：
37.8
作者：
Lin, KM;Lin, B;Dillmann, WH
通讯作者：
Dillmann, WH
影响因子：
64.8
作者：
Zhao, Y;Samal, E;Srivastava, D
通讯作者：
Srivastava, D