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. © FASEB.

Local expression of IGF-1 accelerates muscle regeneration by rapidly modulating inflammatory cytokines and chemokines / Pelosi, Laura; Giacinti, Cristina; C., Nardis; G., Borsellino; Rizzuto, Emanuele; Nicoletti, Carmine; F., Wannenes; L., Battistini; N., Rosenthal; Molinaro, Mario; Musaro', Antonio. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 21:7(2007), pp. 1393-1402. [10.1096/fj.06-7690com]

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

PELOSI, LAURA;GIACINTI, Cristina;RIZZUTO, EMANUELE;NICOLETTI, CARMINE;MOLINARO, Mario;MUSARO', Antonio
2007

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. © FASEB.
2007
fibrosis; inflammatory response; injury
01 Pubblicazione su rivista::01a Articolo in rivista
Local expression of IGF-1 accelerates muscle regeneration by rapidly modulating inflammatory cytokines and chemokines / Pelosi, Laura; Giacinti, Cristina; C., Nardis; G., Borsellino; Rizzuto, Emanuele; Nicoletti, Carmine; F., Wannenes; L., Battistini; N., Rosenthal; Molinaro, Mario; Musaro', Antonio. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 21:7(2007), pp. 1393-1402. [10.1096/fj.06-7690com]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/361171
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