Lin Junfei, Cai Yong, Wang Jian, Liu Ruiqi, Qiu Chong, Huang Yan, Liu Boya, Yang Xiaoming, Zhou Songlin, Shen Yuntian, Wang Wei, Zhu Jianwei
Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, P. R. China.
Department of Neurology, Binhai County People's Hospital, Yancheng, Jiangsu Province, 224500, P. R. China.
Mol Biol Rep. 2023 Dec 12;51(1):9. doi: 10.1007/s11033-023-08952-x.
Complex pathophysiological changes accompany denervation-induced skeletal muscle atrophy, but no effective treatment strategies exist. Our previous study indicated that extracellular vesicles derived from skin-derived precursors-derived Schwann cells (SKP-SC-EVs) can effectively mitigate denervation-induced muscle atrophy. However, the specific molecular mechanism remains unclear.
In this study, we used bioinformatics methods to scrutinize the impact of SKP-SC-EVs on gene expression in denervation-induced skeletal muscle atrophy. We found that SKP-SC-EVs altered the expression of 358 genes in denervated skeletal muscles. The differentially expressed genes were predominantly participated in biological processes, including cell cycle, inflammation, immunity, and adhesion, and signaling pathways, such as FoxO and PI3K.Using the Molecular Complex Detection (MCODE) plugin, we identified the two clusters with the highest score: cluster 1 comprised 37 genes, and Cluster 2 consisted of 24 genes. Then, fifty hub genes were identified using CytoHubba. The intersection of Hub genes and genes obtained by MCODE showed that all 23 genes related to the cell cycle in Cluster 1 were hub genes, and 5 genes in Cluster 2 were hub genes and associated with inflammation.
Overall, the differentially expressed genes in denervated skeletal muscle following SKP-SC-EVs treatment are primarily linked to the cell cycle and inflammation. Consequently, promoting proliferation and inhibiting inflammation may be the critical process in which SKP-SC-EVs delay denervation-induced muscle atrophy. Our findings contribute to a better understanding of the molecular mechanism of SKP-SC-EVs delaying denervation-induced muscle atrophy, offering a promising new avenue for muscle atrophy treatment.
去神经支配诱导的骨骼肌萎缩伴随着复杂的病理生理变化，但目前尚无有效的治疗策略。我们之前的研究表明，源自皮肤衍生前体细胞的施万细胞胞外囊泡（SKP-SC-EVs）可以有效减轻去神经支配诱导的肌肉萎缩。然而，具体的分子机制仍不清楚。
在本研究中，我们使用生物信息学方法来研究SKP-SC-EVs对去神经支配诱导的骨骼肌萎缩中基因表达的影响。我们发现SKP-SC-EVs改变了去神经支配的骨骼肌中358个基因的表达。差异表达基因主要参与包括细胞周期、炎症、免疫和黏附等生物学过程，以及诸如FoxO和PI3K等信号通路。使用分子复合物检测（MCODE）插件，我们鉴定出得分最高的两个聚类：聚类1包含37个基因，聚类2由24个基因组成。然后，使用CytoHubba鉴定出50个枢纽基因。枢纽基因与通过MCODE获得的基因的交集表明，聚类1中所有与细胞周期相关的23个基因都是枢纽基因，聚类2中有5个基因是枢纽基因且与炎症相关。
总体而言，SKP-SC-EVs处理后去神经支配的骨骼肌中的差异表达基因主要与细胞周期和炎症相关。因此，促进增殖和抑制炎症可能是SKP-SC-EVs延缓去神经支配诱导的肌肉萎缩的关键过程。我们的研究结果有助于更好地理解SKP-SC-EVs延缓去神经支配诱导的肌肉萎缩的分子机制，为肌肉萎缩治疗提供了一条有前景的新途径。
