Altered Expression of the MicroRNAS and Their Potential Target Genes in the Soleus Muscle After Peripheral Denervation and Reinnervation in Rats

Abstract

To profile the expression of microRNAs (miRNAs) and their potential target genes in the soleus muscles after denervation and reinnervation of the sciatic nerve in rats. The 4 months denervated and reinnervated soleus muscles were analyzed with Agilent Rat miRNA array to detect the expressed miRNAs against those from the sham control. These differentially expressed miRNAs were applied for hierarchical cluster analysis using average linkage and Pearson correlation as a measure of similarity. A combined approach using computational prediction by the miRanda algorithm and the Agilent Whole Rat Genome 4× 44K oligo microarray experiment was performed to identify the potential target genes of these up-regulated miRNAs. Gene ontology (GO) analysis of these potential target genes into one of the three ontologies, biological process, molecular function, or cellular component, was performed and compared between the denervated and reinnervated muscles. Thirty-six and 39 miRNAs of 350 rat miRNAs tested were significantly up-regulated in the denervated and reinnervated muscles, respectively. The expressed miRNAs in these two groups were similar but with different folds, and the unsupervised hierarchy clustering was able to separate the samples into denervation and reinnervation groupings. In the GO analysis, all three categories indicated a considerable reduced number of the potential target genes of the up-regulated miRNAs and less fraction of differentially expressed genes in most of the GO terms in the reinnervated muscle. This study demonstrated a different involvement of miRNAs and their potential target genes in the soleus muscle after denervation and after reinnervation of the sciatic nerve in a rat model.