Denervation dynamically regulates integrin alpha7 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 alpha7 provoke cell binding and signaling pathways within myofibers. Expression profiles of integrin alpha7 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 alpha7, integrin downstream signaling pathway (Ras or Raf or, ERK1/2), Akt, cleaved caspase-3, fast myosin heavy chain (MHC), beta 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.


CONCLUSIONS
Our novel finding showed that time-series alterations of integrin alpha7 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.
Center for Mathematical Biology, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, and Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan.
Feng-Chou
FC
Tsai
Man-Hui
MH
Pai
Chong-Chi
CC
Chiu
Chih-Ming
CM
Chou
Ming-Shium
MS
Hsieh
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D015153:Blotting, Western; D005260:Female; D039001:Integrin alpha Chains / Q000096:biosynthesis / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000000981:diagnostic imaging / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D016133:Polymerase Chain Reaction; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D014463:Ultrasonography
D015703:Antigens, CD; D039001:Integrin alpha Chains; C085725:integrin alpha7