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.
journal_name
Front Physioljournal_title
Frontiers in physiologyauthors
Shen Y,Zhang R,Xu L,Wan Q,Zhu J,Gu J,Huang Z,Ma W,Shen M,Ding F,Sun Hdoi
10.3389/fphys.2019.01298subject
Has Abstractpub_date
2019-10-11 00:00:00pages
1298issn
1664-042Xjournal_volume
10pub_type
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