Microarray Analysis of Gene Expression Provides New Insights Into Denervation-Induced Skeletal Muscle Atrophy

Yuntian Shen; Ru Zhang; Liang Xu; Qiuxian Wan; Jianwei Zhu; Jing Gu; Ziwei Huang; Wenjing Ma; Mi Shen; Fei Ding; Hualin Sun

doi:10.3389/fphys.2019.01298

Microarray Analysis of Gene Expression Provides New Insights Into Denervation-Induced Skeletal Muscle Atrophy

Front Physiol. 2019 Oct 11:10:1298. doi: 10.3389/fphys.2019.01298. eCollection 2019.

Authors

Yuntian Shen¹, Ru Zhang², Liang Xu³, Qiuxian Wan⁴, Jianwei Zhu⁵, Jing Gu⁴, Ziwei Huang¹, Wenjing Ma¹, Mi Shen¹, Fei Ding¹, Hualin Sun¹

Affiliations

¹ Key Laboratory of Neuroregeneration of Jiangsu, Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
² The Second Affiliated Hospital of Nantong University, Nantong University, Nantong, China.
³ Department of Surgery, Changshu Affiliated Hospital of Nanjing University of Chinese Medicine, Changshu Traditional Chinese Medicine Hospital, Changshu, China.
⁴ Department of Medical Laboratory, School of Public Health, Nantong University, Nantong, China.
⁵ Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, China.

Abstract

Denervation induces skeletal muscle atrophy, accompanied by complex biochemical and physiological changes, with potentially devastating outcomes even an increased mortality. Currently, however, there remains a paucity of effective strategies to treat skeletal muscle atrophy. Therefore, it is required to understand the molecular mechanisms of skeletal muscle atrophy and formulate new treatment strategies. In this study, we investigated the transcriptional profile of denervated skeletal muscle after peripheral nerve injury in rats. The cDNA microarray analysis showed that a huge number of genes in tibialis anterior (TA) muscles were differentially expressed at different times after sciatic nerve transection. Notably, the 24 h of denervation might be a critical time point for triggering TA muscle atrophy. According to the data from self-organizing map (SOM), Pearson correlation heatmap, principal component analysis (PCA), and hierarchical clustering analysis, three nodal transitions in gene expression profile of the denervated TA muscle might partition the period of 0.25 h-28 days post nerve injury into four distinct transcriptional phases. Moreover, the four transcriptional phases were designated as "oxidative stress stage", "inflammation stage", "atrophy stage" and "atrophic fibrosis stage", respectively, which was concluded from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analyses at each transcriptional phase. Importantly, the differentially expressed genes at 24 h post sciatic nerve transection seemed to be mainly involved in inflammation, which might be a critical process in denervation-induced muscle atrophy. Overall, our study would contribute to the understanding of molecular aspects of denervation-induced muscle atrophy, and may also provide a new insight into the time window for targeted therapy.

Keywords: bioinformatics; denervation; inflammation; microarray; oxidative stress; skeletal muscle atrophy.