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      Electroacupuncture inhibits inflammatory injury by targeting the miR-9-mediated NF-κB signaling pathway following ischemic stroke

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          Abstract

          The aim of the present study was to investigate the neuroprotective mechanism of the miR-9-mediated activation of the nuclear factor (NF)-κB signaling pathway by electroacupuncture (EA) stimulation of the Quchi (LI11) and Zusanli (ST36) acupoints in a rat model of middle cerebral artery occlusion (MCAO). The present study demonstrated that EA alleviated the symptoms of neurological deficits and reduced the infarct volume in the rat brains. The expression of miR-9 in the peri-infarct cortex was increased in the EA group compared with the MCAO group, and the expression of NF-κB signaling pathway-associated factors, NF-κB p65, tumor necrosis factor (TNF)-α and interleukin (IL)-1β were reduced. Notably, miR-9 inhibitors were revealed to have the ability to suppress EA-alleviated cerebral inflammation and the expression of NF-κB downstream-related factors, NF-κB p65, TNF-α and IL-1β, and caused no alteration on the level of NF-κB upstream-related protein inhibitor of κBα, suggesting that the cerebral protective efficacy of EA targets miR-9-mediated NF-κB downstream pathway following ischemic stroke.

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          Most cited references27

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          Specificity of microRNA target selection in translational repression.

          MicroRNAs (miRNAs) are a class of noncoding RNAs found in organisms as evolutionarily distant as plants and mammals, yet most of the mRNAs they regulate are unknown. Here we show that the ability of an miRNA to translationally repress a target mRNA is largely dictated by the free energy of binding of the first eight nucleotides in the 5' region of the miRNA. However, G:U wobble base-pairing in this region interferes with activity beyond that predicted on the basis of thermodynamic stability. Furthermore, an mRNA can be simultaneously repressed by more than one miRNA species. The level of repression achieved is dependent on both the amount of mRNA and the amount of available miRNA complexes. Thus, predicted miRNA:mRNA interactions must be viewed in the context of other potential interactions and cellular conditions.
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            Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.

            The tumor suppressor PDCD4 is a proinflammatory protein that promotes activation of the transcription factor NF-kappaB and suppresses interleukin 10 (IL-10). Here we found that mice deficient in PDCD4 were protected from lipopolysaccharide (LPS)-induced death. The induction of NF-kappaB and IL-6 by LPS required PDCD4, whereas LPS enhanced IL-10 induction in cells lacking PDCD4. Treatment of human peripheral blood mononuclear cells with LPS resulted in lower PDCD4 expression, which was due to induction of the microRNA miR-21 via the adaptor MyD88 and NF-kappaB. Transfection of cells with a miR-21 precursor blocked NF-kappaB activity and promoted IL-10 production in response to LPS, whereas transfection with antisense oligonucleotides to miR-21 or targeted protection of the miR-21 site in Pdcd4 mRNA had the opposite effect. Thus, miR-21 regulates PDCD4 expression after LPS stimulation.
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              • Abstract: found
              • Article: not found

              Transcription and processing of human microRNA precursors.

              MicroRNAs have recently emerged as key posttranscriptional regulators of eukaryotic gene expression, yet our understanding of how microRNA expression is itself controlled has remained rudimentary. This review describes recent insights into the mechanisms governing microRNA transcription and processing in vertebrates and their implications for understanding the regulation of microRNA biogenesis.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                February 2016
                30 December 2015
                30 December 2015
                : 13
                : 2
                : 1618-1626
                Affiliations
                [1 ]College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
                [2 ]Fujian Rehabilitation Tech Co-innovation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
                [3 ]Fujian Rehabilitation Engineering Research Center & Fujian Key Lab of Motor Function Rehabilitation, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
                Author notes
                Correspondence to: Mrs. Jing Tao or Professor Lidian Chen, College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, 1 Huatuo Road, Fuzhou, Fujian 350122, P.R. China, E-mail: 369049101@ 123456qq.com , E-mail: fjtcm1958@ 123456sina.com
                Article
                mmr-13-02-1618
                10.3892/mmr.2015.4745
                4732826
                26718002
                4a8aadfc-7f07-499c-a35a-1b9991197259
                Copyright: © Liu et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 31 January 2015
                : 08 December 2015
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                electroacupuncture,ischemic stoke,mir-9,nf-κb signaling pathway

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