Prolonged unloading of rat soleus muscle causes distinct adaptations of the gene profile.

Using commercially available microarray technology, we investigated a series of transcriptional adaptations caused by atrophy of rat m. soleus due to 35 days of hindlimb suspension. We detected 395 out of 1,200 tested transcripts, which reflected 1%-5% of totally expressed genes. From various cellular functional pathways, we detected multiple genes that spanned a 200-fold range of gene expression levels. Statistical analysis combining L1 regression with the sign test based on the conservative Bonferroni correction identified 105 genes that underwent transcriptional adaptations with atrophy. Generally, expressional changes were discrete (<50%) and pointed in the same direction for genes belonging to the same cellular functional units. In particular, a distinct expressional adaptation of genes involved in fiber transformation; that is, metabolism, protein turnover, and cell regulation were noted and matched to corresponding transcriptional changes in nutrient trafficking. Expressional changes of extracellular proteases, and of genes involved in nerve-muscle interaction and excitation-contraction coupling identify previously not recognized adaptations that occur in atrophic m. soleus. Considerations related to technical and statistical aspects of the array approach for profiling the skeletal muscle genome and the impact of observed novel adaptations of the m. soleus transcriptome are put into perspective of the physiological adaptations occurring with muscular atrophy.