title: Repeated muscle biopsies through a single skin incision do not elicit muscle signaling, but IL-6 mRNA and STAT3 phosphorylation increase in injured muscle.
abstract: To determine if muscle biopsies can be repeated using a single small (5-6 mm) skin incision without inducing immediate MAPK activation or inflammation in the noninjured areas, the phosphorylation of ERK1/2, p38-MAPK, c-Jun NH(2)-terminal kinases (JNKs), IκBα, IKKα, and signal transducer and activator of transcription 3 (STAT3) was examined concurrent with IL-6 mRNA in six muscle biopsies obtained from the vastus lateralis of five men. Four biopsies were obtained through the same incision (5-6 mm) from the right leg (taken at 0, 30, 123, and 126 min) and another two each from new incisions performed in the left leg (at 31 and 120 min), while the subjects rested supine. The first three biopsies from the right leg were taken ∼3 cm apart from prebiopsied areas. The last biopsy was obtained from the same point from which the second biopsy was sampled. The three biopsies performed through the same skin incision from noninjured muscle areas showed similar levels of ERK1/2, p38-MAPK, JNK, IKKα, IκBα, and STAT3 phosphorylation and similar IL-6 mRNA content. There were no significant differences in the levels of ERK1/2, p38-MAPK, JNK, IKKα, and IκBα phosphorylation between the mean of the three biopsies obtained from the same incision and the sixth biopsy obtained from an injured area. STAT3 phosphorylation was increased by ∼3.5-fold in the sixth biopsy compared with the mean the three biopsies obtained from the same incision (P < 0.05), and IL-6 mRNA content was increased by 1.8-fold (P < 0.05). In summary, repeated muscle biopsies can be performed through a single 5- to 6-mm skin incision without eliciting muscle signaling through cascades responding to cellular stress, inflammation, or muscle damage. STAT3 phosphorylation is an early event in the healing response to muscle injury, probably mediated by the autocrine production of IL-6.
authors: Departamento de Educación Física, Campus Universitario de Tafira, 35017 Las Palmas de Gran Canaria, Canary Island, Spain.
authors: Borja
authors: B
authors: Guerra
authors: M Carmen
authors: MC
authors: Gómez-Cabrera
authors: Jesús Gustavo
authors: JG
authors: Ponce-González
authors: Vladimir E
authors: VE
authors: Martinez-Bello
authors: Amelia
authors: A
authors: Guadalupe-Grau
authors: Alfredo
authors: A
authors: Santana
authors: Vicente
authors: V
authors: Sebastia
authors: Jose
authors: J
authors: Viña
authors: José A L
authors: JA
authors: Calbet
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001706:Biopsy / Q000009:adverse effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009135:Muscular Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D052097:Quadriceps Muscle / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation; D014945:Wound Healing; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000072000:NF-KappaB Inhibitor alpha; C496559:CHUK protein, human; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases