Kim NaJung, Yoo James J, Atala Anthony, Lee Sang Jin
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
FASEB J. 2016 Mar;30(3):1198-206. doi: 10.1096/fj.15-271809. Epub 2015 Dec 1.
Selectively controlling the expression of the target genes through RNA interference (RNAi) has significant therapeutic potential for injuries or diseases of tissues. We used this strategy to accelerate and enhance skeletal muscle regeneration for the treatment of muscular atrophy. In this study, we used myostatin small interfering (si)RNA (siGDF-8), a major inhibitory factor in the development and postnatal regeneration of skeletal muscle and muscle-specific microRNAs (miR-1 and -206) to further accelerate muscle regeneration. This combination of 3 small RNAs significantly improved the gene expression of myogenic regulatory factors in vitro, suggesting myogenic activation. Moreover, cell proliferation and myotube formation improved without compromising each other, which indicates the myogenic potential of this combination of small RNAs. The recovery of chemically injured tibialis anterior muscles in rats was significantly accelerated, both functionally and structurally. This novel combination of siRNA and miRNAs has promising therapeutic potential to improve in situ skeletal muscle regeneration.
通过RNA干扰（RNAi）选择性地控制靶基因的表达对于组织损伤或疾病具有显著的治疗潜力。我们采用这种策略来加速和增强骨骼肌再生，以治疗肌肉萎缩。在本研究中，我们使用肌肉生长抑制素小干扰（si）RNA（siGDF - 8），它是骨骼肌发育和出生后再生过程中的主要抑制因子，以及肌肉特异性微小RNA（miR - 1和 - 206）来进一步加速肌肉再生。这三种小RNA的组合在体外显著改善了生肌调节因子的基因表达，提示生肌激活。此外，细胞增殖和肌管形成均得到改善且互不影响，这表明这种小RNA组合具有生肌潜力。大鼠化学损伤的胫前肌在功能和结构上的恢复均显著加速。这种siRNA和miRNA的新型组合在改善原位骨骼肌再生方面具有广阔的治疗潜力。
