Regulation of alpha7 integrin by mechanical stress during skeletal muscle regeneration

The continuity of the tendon-myofibre-tendon units disrupted by shearing injury must be re-established during regeneration. We have previously demonstrated in freely moving rats that transected myofibres reinforce their lateral integrin-mediated adhesion, with the maximum around days 5-7. After day 14, most integrin molecules are redistributed to the newly formed myotendinous junctions, by which the ends of regenerating myofibres attach to the scar between the stumps. Here, we analyzed the effects of mechanical stress (free and forced mobilization vs. immobilization and denervation separately and in combination) on the expression of alpha7 integrin and merosin in regenerating myofibres using quantitative in situ hybridization and immunohistochemistry. In all groups, alpha7 integrin expression was upregulated at mRNA level, whereas increased protein accumulation in lateral sarcolemma occurred only in the mobilized groups. The accumulation of merosin was not affected by the stress level. The results demonstrate that active mechanical stress reinforces early lateral integrin-mediated adhesion; molecules may at the same time mediate signals from matrix to cells for adaptation to the altered biomechanical status.