The Signature of MicroRNA Dysregulation in Muscle Paralyzed by Spinal Cord Injury Includes Downregulation of MicroRNAs that Target Myostatin Signaling.
The Signature of MicroRNA Dysregulation in Muscle Paralyzed by Spinal Cord Injury Includes Downregulation of MicroRNAs that Target Myostatin Signaling.
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DOI：
10.1371/journal.pone.0166189
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Cardozo CP
中科院分区：
文献类型：
--
作者：
De Gasperi R;Graham ZA;Harlow LM;Bauman WA;Qin W;Cardozo CP
脊髓损伤(SCI)导致肌肉萎缩、力量生成减少和氧化-糖酵解纤维类型转变。导致这些变化的机制仍然不完全清楚。为了对脊髓损伤后肌肉恶化的机制有新的认识，比较了假手术(Sham)和脊髓横断(SCI)大鼠瘫痪腓肠肌miRs的整体表达谱。对改变的MIR的独创性路径分析发现，通过胰岛素、胰岛素样生长因子-1、整合素和转化生长因子-β的信号显著丰富了目标基因。定量聚合酶链式反应显示，脊髓损伤后56天，骨骼肌中miR23a、23b、27b、145和206的表达均下调。利用FISH，miR-145，一种以前没有涉及骨骼肌功能的miR，被发现定位于骨骼肌纤维。MiR-145的一个预测靶点是Cited2，它是一种转录调控因子，通过NF-κB、Smad3和其他转录因子调节信号。Cited2基因的3‘非编码区含有高度保守的miR-145种子序列。荧光素酶分析证实miR-145与该种子序列相互作用。然而，假手术组和脊髓损伤组之间的Cited2蛋白水平相似，表明在脊髓损伤后的适应环境中没有涉及到生化相互作用。综上所述，这些发现表明脊髓损伤后骨骼肌中几个高表达的miR的失调，并提示miR-23a、145和206的表达减少可能在上运动神经元损伤所致的骨骼肌质量和胰岛素反应性的改变中起作用。
Spinal cord injury (SCI) results in muscle atrophy, reduced force generation and an oxidative-to-glycolytic fiber type shift. The mechanisms responsible for these alterations remain incompletely understood. To gain new insights regarding mechanisms involved in deterioration of muscle after SCI, global expression profiles of miRs in paralyzed gastrocnemius muscle were compared between sham-operated (Sham) and spinal cord-transected (SCI) rats. Ingenuity Pathways Analysis of the altered miRs identified signaling via insulin, IGF-1, integrins and TGF-β as being significantly enriched for target genes. By qPCR, miRs 23a, 23b, 27b, 145, and 206, were downregulated in skeletal muscle 56 days after SCI. Using FISH, miR-145, a miR not previously implicated in the function of skeletal muscle, was found to be localized to skeletal muscle fibers. One predicted target of miR-145 was Cited2, a transcriptional regulator that modulates signaling through NF-κB, Smad3 and other transcription factors. The 3’ UTR of Cited2 mRNA contained a highly conserved miR-145 seed sequence. Luciferase reporter assays confirmed that miR-145 interacts with this seed sequence. However, Cited2 protein levels were similar between Sham and SCI groups, indicating a biochemical interaction that was not involved in the context of adaptations after SCI. Taken together, the findings indicate dysregulation of several highly expressed miRs in skeletal muscle after SCI and suggest that reduced expression of miR-23a, 145 and 206 may have roles in alteration in skeletal muscle mass and insulin responsiveness in muscle paralyzed by upper motor neuron injuries.
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DOI：
10.12659/msm.897909
发表时间：
2016-04-07
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Huang QK;Qiao HY;Fu MH;Li G;Li WB;Chen Z;Wei J;Liang BS
通讯作者：
Liang BS
DOI：
10.1016/j.biocel.2013.06.011
发表时间：
2013-10
影响因子：
4
作者：
Bodine, Sue C.
通讯作者：
Bodine, Sue C.
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
29
作者：
Kunkel SD;Suneja M;Ebert SM;Bongers KS;Fox DK;Malmberg SE;Alipour F;Shields RK;Adams CM
通讯作者：
Adams CM
影响因子：
8
作者：
Chou, Y-T;Wang, H.;Yang, Y-C
通讯作者：
Yang, Y-C