title: The neurotrophin receptor p75NTR is induced on mature myofibres in inflammatory myopathies and promotes myotube survival to inflammatory stress.
abstract: OBJECTIVE
  Recent studies propose the neurotrophin receptor p75NTR as a marker for muscle satellite cells and a key regulator of regenerative processes after injury. Here, we investigated the contribution of cellular compartments other than satellite cells and regenerating myofibres to p75NTR signal in diseased skeletal muscle.
  
  
  METHODS
  We checked regulation of p75NTR expression in muscle biopsies from patients with inflammatory myopathies (polymyositis, dermatomyositis and inclusion body myositis), or Becker muscular dystrophy, and in nonmyopathic tissues. Quantitative PCR, immunohistochemistry, immunofluorescence or electron microscopy were used. RNA interference approaches were applied to myotubes to explore p75NTR function.
  
  
  RESULTS
  We found p75NTR transcript and protein upregulation in all inflammatory myopathies but not in dystrophic muscle, suggesting a role for inflammatory mediators in induction of p75NTR expression. In inflamed muscle p75NTR was localized on distinct cell types, including immune cells and mature myofibres. In vitro assays on human myotubes confirmed that inflammatory factors such as IL-1 could induce p75NTR. Finally, RNA interference experiments in differentiated cells showed that, in the absence of p75NTR, myotubes were more susceptible to apoptosis when exposed to inflammatory stimuli.
  
  
  CONCLUSIONS
  Our observations that p75NTR is upregulated on skeletal myofibres in inflammatory myopathies in vivo and promotes resistance to inflammatory mediators in vitro suggest that neurotrophin signalling through p75NTR may mediate a tissue-protective response to inflammation in skeletal myofibres.
authors.affiliation: Neuroimmunology and Neuromuscular Disorders, Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Colombo
authors.forename: S
authors.initials: S
authors.lastname: Romaggi
authors.forename: F
authors.initials: F
authors.lastname: Blasevich
authors.forename: M
authors.initials: M
authors.lastname: Mora
authors.forename: C
authors.initials: C
authors.lastname: Falcone
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
authors.forename: L
authors.initials: L
authors.lastname: Morandi
authors.forename: C
authors.initials: C
authors.lastname: Farina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002470:Cell Survival; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D009210:Myofibrils / Q000378:metabolism* / Q000473:pathology; D009220:Myositis / Q000378:metabolism* / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: C484065:NGFR protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor