Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi, P. R. China.
State Key Laboratory of Solidification Processing, Northwestern Polytechnical University, Xi'an 710072, Shaanxi, P. R. China.
Mol Pharm. 2021 Aug 2;18(8):2959-2973. doi: 10.1021/acs.molpharmaceut.1c00121. Epub 2021 Jun 30.
Muscle atrophy usually occurs under mechanical unloading, which increases the risk of injury to reduce the functionality of the moving system, while there is still no effective therapy until now. It was found that miR-194 was significantly downregulated in a muscle atrophy model, and its target protein was the myocyte enhancer factor 2C (MEF2C). miR-194 could promote muscle differentiation and also inhibit ubiquitin ligases, thus miR-194 could be used as a nucleic acid drug to treat muscle atrophy, whereas miRNA was unstable , limiting its application as a therapeutic drug. A gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA here. Exogenous miR-194 was loaded in GNs and injected into the muscle atrophy model. It demonstrated that the muscle fiber cross-sectional area, in situ muscle contractile properties, and myogenic markers were increased significantly after treatment. It proposed miR-194 loaded in GNs as an effective treatment for muscle atrophy by promoting muscle differentiation and inhibiting ubiquitin ligase activity. Moreover, the developed miRNA delivery system, taking advantage of its tunable composition, degradation rate, and capacity to load various drug molecules with high dosage, is considered a promising platform to achieve precise treatment of muscle atrophy-related diseases.
肌肉萎缩通常发生在机械卸载下，这增加了受伤的风险，降低了运动系统的功能，而到目前为止还没有有效的治疗方法。研究发现，在肌肉萎缩模型中 miR-194 显著下调，其靶蛋白是肌细胞增强因子 2C（MEF2C）。miR-194 可以促进肌肉分化，同时抑制泛素连接酶，因此 miR-194 可以作为一种核酸药物来治疗肌肉萎缩，而 miRNA 不稳定，限制了其作为治疗药物的应用。这里首次应用明胶纳米球（GN）传递系统来负载外源性 miRNA。将外源性 miR-194 装载到 GN 中并注射到肌肉萎缩模型中。结果表明，治疗后肌肉纤维横截面积、原位肌肉收缩性能和生肌标志物显著增加。提出装载在 GN 中的 miR-194 通过促进肌肉分化和抑制泛素连接酶活性，作为肌肉萎缩的有效治疗方法。此外，开发的 miRNA 传递系统利用其可调组成、降解率以及高剂量装载各种药物分子的能力，被认为是实现肌肉萎缩相关疾病精确治疗的有前途的平台。
