Insulin-like growth factor I in inclusion-body myositis and human muscle cultures

Aldobrando Broccolini, Enzo Ricci, Mario Pescatori, Manuela Papacci, Carla Gliubizzi, Adele D'Amico, Serenella Servidei, Pietro Tonali, Massimiliano Mirabella

Research output: Contribution to journalArticlepeer-review

Abstract

Possible pathogenic mechanisms of sporadic inclusion-body myositis (sIBM) include abnormal production and accumulation of amyloid β (Aβ), muscle aging, and increased oxidative stress. Insulin-like growth factor I (IGF-I), an endocrine and autocrine/paracrine trophic factor, provides resistance against Aβ toxicity and oxidative stress in vitro and promotes cell survival. In this study we analyzed the IGF-I signaling pathway in sIBM muscle and found that 16.2% ± 2.5% of nonregenerating fibers showed increased expression of IGF-I, phosphatidylinositide 3′OH-kinase, and Akt. In the majority of sIBM abnormal muscle fibers, increased IGF-I mRNA and protein correlated with the presence of Aβ cytoplasmic inclusions. To investigate a possible relationship between Aβ toxicity and IGF-I upregulation, normal primary muscle cultures were stimulated for 24 hours with the Aβ(25-35) peptide corresponding to the biologically active domain of Aβ. This induced an increase of IGF-I mRNA and protein in myotubes at 6 hours, followed by a gradual reduction thereafter. The level of phosphorylated Akt showed similar changes. We suggest that in sIBM, IGF-I overexpression represents a reactive response to Aβ toxicity, possibly providing trophic support to vulnerable fibers. Understanding the signaling pathways activated by IGF-I in sIBM may lead to novel therapeutic strategies for the disease.

Original languageEnglish
Pages (from-to)650-659
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume63
Issue number6
Publication statusPublished - Jun 2004

Keywords

  • β-Amyloid
  • Inclusion-body myositis
  • Insulin-like growth factor
  • Muscle cultures

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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