title: Nitric oxide regulates the repair of injured skeletal muscle.
abstract: Skeletal muscle repair can be understood as a balance between fibrosis and regeneration, the result of which may lead to complete recovery or loss of muscle function. To study the involvement of nitric oxide in post-trauma muscle repair, we used an experimental murine model of crush injury muscle. The animals were divided into four groups, (i) control (CO), (ii) sham trauma, (iii) trauma and (iv) trauma+l-NAME. The animals received a single dose of 100mg/kg of the l-NAME, an inhibitor of nitric oxide synthase, 2h after lesion, and the muscle tissue was analyzed in two time-points: 24h and 7 days. Twenty-four hours after injury, the crushed muscle was characterized by an intense inflammatory cell infiltrate and edema demonstrated by histological analysis. These changes were accompanied by increased iNOS, MMP-2 and HGF mRNA transcription and protein expression of the iNOS and MMP-2 in the gastrocnemius muscle. Crushing injury also promoted cell proliferation and increase number satellite cell, responsible for the regeneration of the muscle fiber. Treatment with l-NAME blocking local NO production, greatly attenuated these histological and molecular findings at 24h. On the 7th day the molecular findings of both groups were comparable to the control (sham trauma) group. However, the l-NAME group showed increase deposition of collagen and decrease of SC expression. These findings demonstrate that activation of NO during muscle crush is critical in the early phases of the skeletal muscle repair process and indicate its possible role as a regulator of the balance between fibrosis and muscle regeneration.
authors.affiliation: Serviço de Reumatologia do Hospital de Clínicas de Porto Alegre (HCPA) - e Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Lidiane Isabel
authors.initials: LI
authors.lastname: Filippin
authors.forename: María José
authors.initials: MJ
authors.lastname: Cuevas
authors.forename: Elena
authors.initials: E
authors.lastname: Lima
authors.forename: Norma Possa
authors.initials: NP
authors.lastname: Marroni
authors.forename: Javier
authors.initials: J
authors.lastname: Gonzalez-Gallego
authors.forename: Ricardo Machado
authors.initials: RM
authors.lastname: Xavier
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D051763:PAX7 Transcription Factor; D009569:Nitric Oxide; D017228:Hepatocyte Growth Factor; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; D020778:Matrix Metalloproteinase 2; D019331:NG-Nitroarginine Methyl Ester