The neurotrophin receptor p75NTR is induced on mature myofibres in inflammatory myopathies and promotes myotube survival to inflammatory stress

E. Colombo, S. Romaggi, F. Blasevich, M. Mora, C. Falcone, H. Lochmüller, L. Morandi, C. Farina

Research output: Contribution to journalArticle

Abstract

Aims: 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.

Original languageEnglish
Pages (from-to)367-378
Number of pages12
JournalNeuropathology and Applied Neurobiology
Volume38
Issue number4
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Nerve Growth Factor Receptors
Myositis
Skeletal Muscle Fibers
RNA Interference
Muscles
Inclusion Body Myositis
Dermatomyositis
Duchenne Muscular Dystrophy
Nerve Growth Factors
Interleukin-1
Fluorescence Microscopy
Muscle Cells
Electron Microscopy
Skeletal Muscle
Up-Regulation
Immunohistochemistry
Apoptosis
Inflammation
Biopsy
Polymerase Chain Reaction

Keywords

  • Human skeletal muscle
  • Inflammation
  • Myositis
  • P75NTR

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neurology
  • Histology
  • Physiology (medical)

Cite this

The neurotrophin receptor p75NTR is induced on mature myofibres in inflammatory myopathies and promotes myotube survival to inflammatory stress. / Colombo, E.; Romaggi, S.; Blasevich, F.; Mora, M.; Falcone, C.; Lochmüller, H.; Morandi, L.; Farina, C.

In: Neuropathology and Applied Neurobiology, Vol. 38, No. 4, 06.2012, p. 367-378.

Research output: Contribution to journalArticle

@article{112599e7a2234e7ebf408f69bf95f755,
title = "The neurotrophin receptor p75NTR is induced on mature myofibres in inflammatory myopathies and promotes myotube survival to inflammatory stress",
abstract = "Aims: 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.",
keywords = "Human skeletal muscle, Inflammation, Myositis, P75NTR",
author = "E. Colombo and S. Romaggi and F. Blasevich and M. Mora and C. Falcone and H. Lochm{\"u}ller and L. Morandi and C. Farina",
year = "2012",
month = "6",
doi = "10.1111/j.1365-2990.2011.01212.x",
language = "English",
volume = "38",
pages = "367--378",
journal = "Neuropathology and Applied Neurobiology",
issn = "0305-1846",
publisher = "Wiley Blackwell",
number = "4",

}

TY - JOUR

T1 - The neurotrophin receptor p75NTR is induced on mature myofibres in inflammatory myopathies and promotes myotube survival to inflammatory stress

AU - Colombo, E.

AU - Romaggi, S.

AU - Blasevich, F.

AU - Mora, M.

AU - Falcone, C.

AU - Lochmüller, H.

AU - Morandi, L.

AU - Farina, C.

PY - 2012/6

Y1 - 2012/6

N2 - Aims: 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.

AB - Aims: 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.

KW - Human skeletal muscle

KW - Inflammation

KW - Myositis

KW - P75NTR

UR - http://www.scopus.com/inward/record.url?scp=84860899688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860899688&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2990.2011.01212.x

DO - 10.1111/j.1365-2990.2011.01212.x

M3 - Article

C2 - 21851375

AN - SCOPUS:84860899688

VL - 38

SP - 367

EP - 378

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 4

ER -