Denervation dynamically regulates integrin α7 signaling pathways and microscopic structures in rats

Background: Peripheral nerve injury causes serious problems in orthopedic and plastic surgeries. Cell adhesion molecules such as integrin α7 provoke cell binding and signaling pathways within myofibers. Expression profiles of integrin α7 signaling pathways and the molecule's microscopic structure were assessed to investigate the long-term dynamic changes in denervated rat skeletal muscle. Methods: A denervated rat skeletal muscle model was established by severing the sciatic nerve for 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 20 weeks, and 26 weeks. Molecular expressions were investigated by mRNA and Western blot. The structural alterations were detected by immunohistochemistry, scanning electron microscopy, and transmission electron microscopy. Results: The denervated muscle atrophy presented the following dynamic molecular alterations: an initial increase around postdenervation in week (PIW) 8 and then a subsequent decay of integrin α7, integrin downstream signaling pathway (Ras or Raf or, ERK1/2), Akt, cleaved caspase-3, fast myosin heavy chain (MHC), β actin, and RhoA. We demonstrated that the expressions of multiple signaling molecules were highly upregulated at PIW 8 (p <0.01). Scanning electron microscopy findings of the surface textures of myofibers showed more severe damage at PIW 8 and subsequently became smoother. Inner structures of myofibers separated with discontinuity on transmission electron microscopy examinations. Conclusion: Our novel finding showed that time-series alterations of integrin α7 signaling molecules and surface microstructures in the long-term denervated rat skeletal muscle are biphasic and coherently dynamic. Persisted p-Akt elevation suggested that denervated muscle may regenerate if reinnervation or other treatment was performed.