Autoregulation of inducible nitric oxide synthase expression by RNA interference provides neuroprotection in neonatal rats.
Autoregulation of inducible nitric oxide synthase expression by RNA interference provides neuroprotection in neonatal rats.
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作者：
Wang Z;Feng C;Zhao H;Ren X;Peng S;Zuo Z
我们已经证明了在细胞培养中通过RNA干扰自动调节基因表达是可以实现的。为了确定这一新概念是否可用于在活体条件下产生神经保护，出生后第3天(PND)大鼠脑室注射携带或不携带诱导型一氧化氮合酶(INOS)短发夹状RNA(ShRNA)密码子的慢病毒。该shRNA的表达受iNOS启动子(Pinos-shRNA)或巨细胞病毒启动子(pCMV-shRNA)的调控。大鼠于PND7时行脑缺氧缺血模型。缺血区脑组织iNOS表达增加。这种增加被携带Pinos-shRNA的病毒减弱。携带pCMV-shRNA的病毒使iNOS降低到低于对照组的水平。携带Pinos-shRNA的病毒可减轻缺氧缺血后的脑组织损伤和功能损害，但pCMV-shRNA不能减轻缺氧缺血后的脑组织损伤。我们的结果提供了概念验证证据，证明通过RNA干扰自动调节iNOS表达可以诱导体内的神经保护，并且适当的基因表达调节是重要的。
We have shown that autoregulation of gene expression by RNA interference is achievable in cell cultures. To determine whether this novel concept could be used to produce neuroprotection under in vivo condition, postnatal day (PND) 3 rats received intracerebroventricular injection of lentivirus that carried or did not carry code for short hairpin RNA (shRNA) of inducible nitric oxide synthase (iNOS). The expression of this shRNA was controlled by an iNOS promoter (piNOS-shRNA) or cytomegalovirus promoter (pCMV-shRNA). The rats were subjected to brain hypoxia-ischemia at PND7. Ischemic brain tissues had increased iNOS expression. This increase was attenuated by virus carrying piNOS-shRNA. Virus carrying pCMV-shRNA reduced iNOS to a level that was lower than control. Brain tissue loss and functional impairment after the hypoxia-ischemia were attenuated by the virus carrying piNOS-shRNA but not by pCMV-shRNA. Our results provide proof-of-concept evidence that autoregulation of iNOS expression by RNA interference induces neuroprotection in vivo and that appropriate regulation of gene expression is important.
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DOI：
10.4049/jimmunol.1400918
发表时间：
2014-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Garcia-Bonilla L;Moore JM;Racchumi G;Zhou P;Butler JM;Iadecola C;Anrather J
通讯作者：
Anrather J
影响因子：
64.8
作者：
Grimm, Dirk;Streetz, Konrad L.;Kay, Mark A.
通讯作者：
Kay, Mark A.
影响因子：
6.2
作者：
Colin, Angelique;Faideau, Mathilde;Deglon, Nicole
通讯作者：
Deglon, Nicole
影响因子：
3.3
作者：
Li, L.;Zuo, Z.
通讯作者：
Zuo, Z.
影响因子：
5.3
作者：
Kunz, Alexander;Park, Laibaik;Iadecola, Costantino
通讯作者：
Iadecola, Costantino