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首页> 外文期刊>The European Journal of Neuroscience >MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish.
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MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish.

机译：MicroRNA miR-133b对于成年斑马鱼脊髓损伤后的功能恢复至关重要。

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摘要

MicroRNAs (miRNAs) play important roles during development and also in adult organisms by regulating the expression of multiple target genes. Here, we studied the function of miR-133b during zebrafish spinal cord regeneration and show upregulation of miR-133b expression in regenerating neurons of the brainstem after transection of the spinal cord. miR-133b has been shown to promote tissue regeneration in other tissue, but its ability to do so in the nervous system has yet to be tested. Inhibition of miR-133b expression by antisense morpholino (MO) application resulted in impaired locomotor recovery and reduced regeneration of axons from neurons in the nucleus of the medial longitudinal fascicle, superior reticular formation and intermediate reticular formation. miR-133b targets the small GTPase RhoA, which is an inhibitor of axonal growth, as well as other neurite outgrowth-related molecules. Our results indicate that miR-133b is an important determinant in spinal cord regeneration of adult zebrafish through reduction in RhoA protein levels by direct interaction with its mRNA. While RhoA has been studied as a therapeutic target in spinal cord injury, this is the first demonstration of endogenous regulation of RhoA by a microRNA that is required for spinal cord regeneration in zebrafish. The ability of miR-133b to suppress molecules that inhibit axon regrowth may underlie the capacity for adult zebrafish to recover locomotor function after spinal cord injury.
机译：MicroRNA（miRNA）在发育过程中以及在成年生物中都通过调节多个靶基因的表达发挥重要作用。在这里，我们研究了miR-133b在斑马鱼脊髓再生过程中的功能，并显示了脊髓横断后脑干再生神经元中miR-133b表达的上调。已显示miR-133b可以促进其他组织的组织再生，但是其在神经系统中的再生能力尚待测试。反义吗啉代（MO）应用对miR-133b表达的抑制作用导致运动恢复受损，并减少了内侧纵束神经核中轴突再生，上层网状结构和中间网状结构的形成。 miR-133b靶向小的GTPase RhoA，它是轴突生长的抑制剂，以及其他与神经突生长相关的分子。我们的研究结果表明，miR-133b是成年斑马鱼脊髓再生中的重要决定因素，这是通过直接与其mRNA相互作用来降低RhoA蛋白水平的结果。尽管已经研究了RhoA作为脊髓损伤的治疗靶标，但这是斑马鱼脊髓再生所必需的microRNA对RhoA的内源性调节的首次证明。 miR-133b抑制抑制轴突再生的分子的能力可能是成年斑马鱼在脊髓损伤后恢复运动功能的能力的基础。

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