Local expression of IGF-1 accelerates muscle regeneration by rapidly modulating inflammatory cytokines and chemokines

Laura Pelosi, Cristina Giacinti, Chiara Nardis, Giovanna Borsellino, Emanuele Rizzuto, Carmine Nicoletti, Francesca Wannenes, Luca Battistini, Nadia Rosenthal, Mario Molinaro, Antonio Musarò

Research output: Contribution to journalArticlepeer-review

Abstract

Muscle regeneration following injury is characterized by myonecrosis accompanied by local inflammation, activation of satellite cells, and repair of injured fibers. The resolution of the inflammatory response is necessary to proceed toward muscle repair, since persistence of inflammation often renders the damaged muscle incapable of sustaining efficient muscle regeneration. Here, we show that local expression of a muscle-restricted insulin-like growth factor (IGF)-1 (mIGF-1) transgene accelerates the regenerative process of injured skeletal muscle, modulating the inflammatory response, and limiting fibrosis. At the molecular level, mIGF-1 expression significantly down-regulated proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, and modulated the expression of CC chemokines involved in the recruitment of monocytes/macrophages. Analysis of the underlying molecular mechanisms revealed that mIGF-1 expression modulated key players of inflammatory response, such as macrophage migration inhibitory factor (MIF), high mobility group protein-1 (HMGB1), and transcription NF-κB. The rapid restoration of injured mIGF-1 transgenic muscle was also associated with connective tissue remodeling and a rapid recovery of functional properties. By modulating the inflammatory response and reducing fibrosis, supplemental mIGF-1 creates a qualitatively different environment for sustaining more efficient muscle regeneration and repair.

Original languageEnglish
Pages (from-to)1393-1402
Number of pages10
JournalFASEB Journal
Volume21
Issue number7
DOIs
Publication statusPublished - May 2007

Keywords

  • Fibrosis
  • Inflammatory response
  • Injury

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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