Yang Xiaoming, Li Ming, Ji Yanan, Lin Yinghao, Xu Lai, Gu Xiaosong, Sun Hualin, Wang Wei, Shen Yuntian, Liu Hua, Zhu Jianwei
School of Biology and Basic Medical Sciences, Medical College of Soochow University, Suzhou, China.
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-Innovation Center of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China.
Front Physiol. 2022 Jun 24;13:923190. doi: 10.3389/fphys.2022.923190. eCollection 2022.
Peripheral nerve injury is common, and can lead to skeletal muscle atrophy and dysfunction. However, the underlying molecular mechanisms are not fully understood. The transcription factors have been proved to play a key role in denervated muscle atrophy. In order to systematically analyze transcription factors and obtain more comprehensive information of the molecular regulatory mechanisms in denervated muscle atrophy, a new transcriptome survey focused on transcription factors are warranted. In the current study, we used microarray to identify and analyze differentially expressed genes encoding transcription factors in denervated muscle atrophy in a rat model of sciatic nerve dissection. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to explore the biological functions of differentially expressed transcription factors and their target genes related to skeletal muscle pathophysiology. We found that the differentially expressed transcription factors were mainly involved in the immune response. Based on correlation analysis and the expression trends of transcription factors, 18 differentially expressed transcription factors were identified. Stat3, Myod1, Runx1, Atf3, Junb, Runx2, Myf6, Stat5a, Tead4, Klf5, Myog, Mef2a, and Hes6 were upregulated. Ppargc1a, Nr4a1, Lhx2, Ppara, and Rxrg were downregulated. Functional network mapping revealed that these transcription factors are mainly involved in inflammation, development, aging, proteolysis, differentiation, regeneration, autophagy, oxidative stress, atrophy, and ubiquitination. These findings may help understand the regulatory mechanisms of denervated muscle atrophy and provide potential targets for future therapeutic interventions for muscle atrophy following peripheral nerve injury.
周围神经损伤很常见，可导致骨骼肌萎缩和功能障碍。然而，其潜在的分子机制尚未完全明确。转录因子已被证明在失神经支配的肌肉萎缩中起关键作用。为了系统地分析转录因子并获得失神经支配的肌肉萎缩中分子调控机制更全面的信息，有必要开展一项聚焦于转录因子的新转录组研究。在本研究中，我们使用微阵列来鉴定和分析坐骨神经切断大鼠模型中失神经支配的肌肉萎缩中编码转录因子的差异表达基因。利用基因本体论和京都基因与基因组百科全书分析来探索差异表达转录因子及其与骨骼肌病理生理学相关的靶基因的生物学功能。我们发现差异表达转录因子主要参与免疫反应。基于相关性分析和转录因子的表达趋势，鉴定出18个差异表达转录因子。Stat3、Myod1、Runx1、Atf3、Junb、Runx2、Myf6、Stat5a、Tead4、Klf5、Myog、Mef2a和Hes6上调。Ppargc1a、Nr4a1、Lhx2、Ppara和Rxrg下调。功能网络映射显示这些转录因子主要参与炎症、发育、衰老、蛋白水解、分化、再生、自噬、氧化应激、萎缩和泛素化。这些发现可能有助于理解失神经支配的肌肉萎缩的调控机制，并为周围神经损伤后肌肉萎缩的未来治疗干预提供潜在靶点。
