Expression of α7β1 Integrin Splicing Variants during Skeletal Muscle Regeneration

Integrin α7β1 is a laminin receptor, both subunits of which have alternatively spliced, developmentally regulated variants. In skeletal muscle β1 has two major splice variants of the intracellular domain (β1A and β1D). α7×1 and α7×2 represent variants of the α7 ectodomain, whereas α7A and α7B are variants of the intracellular domain. Previously we showed that during early regeneration after transection injury of muscle α7 integrin mediates dynamic adhesion of myofibers along their lateral aspects to the extracellular matrix. Stable attachment of myofibers to the extracellular matrix occurs during the third week after injury, when new myotendinous junctions develop at the ends of the regenerating myofibers. Now we have analyzed the relative expression of β1A/β1D and α7A/α7B and α7×1/α7×2 isoforms during regeneration for 2 to 56 days after transection of rat soleus muscle using reverse transcriptase-polymerase chain reaction and immunohistochemistry. During early regeneration β1A was the predominant isoform in both the muscle and scar tissue. Expression of muscle-specific β1D was detected in regenerating myofibers from day 4 onwards, ie, when myogenic mitotic activity began to decrease, and it became more abundant with the progression of regeneration. α7B isoform predominated on day 2. Thereafter, the relative expression of α7A transcripts increased until day 7 with the concomitant appearance of α7A immunoreactivity on regenerating myofibers. Finally, α7B again became the predominant variant in highly regenerated myofibers. Similarly as in the controls, α7×1 and α7×2 isoforms were both expressed throughout the regeneration with a peak in α7×1 expression on day 4 coinciding with the dynamic adhesion stage. The results suggest that during regeneration of skeletal muscle the splicing of β1 and α7 integrin subunits is regulated according to functional requirements. α7A and α7×1 appear to have a specific role during the dynamic phase of adhesion, whereas α7B, α7×2, and β1D predominate during stable adhesion.