Impaired structural and functional regeneration of skeletal muscles from beta 2-adrenoceptor knockout mice

Autor(es)

Silva, M. T. ^[1] ; Wensing, L. A. ^[2] ; Brum, P. C. ^[3] ; Camara, N. O. ^[2] ; Miyabara, E. H. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Phys Educ & Sport, Dept Biodynam, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ACTA PHYSIOLOGICA; v. 211, n. 4, p. 617-633, AUG 2014.
• Citações Web of Science: 10

Resumo

Aims: beta 2-adrenergic stimulation causes beneficial effects on structure and function of regenerating muscles; thus, the beta 2-adrenoceptor may play an important role in the muscle regenerative process. Here, we investigated the role of the beta 2-adrenoceptor in skeletal muscle regeneration. Methods: Tibialis anterior (TA) muscles from beta 2-adrenoceptor knockout (beta 2KO) mice were cryolesioned and analysed after 1, 3, 10 and 21 days. The role of beta 2-adrenoceptor on regenerating muscles was assessed through the analysis of morphological and contractile aspects, M1 and M2 macrophage profile, cAMP content, and activation of TGF-beta signalling elements. Results: Regenerating muscles from beta 2KO mice showed decreased calibre of regenerating myofibres and reduced muscle contractile function at 10 days when compared with those from wild type. The increase in cAMP content in muscles at 10 days post-cryolesion was attenuated in the absence of the beta 2-adrenoceptor. Furthermore, there was an increase in inflammation and in the number of macrophages in regenerating muscles lacking the beta 2-adrenoceptor at 3 and 10 days, a predominance of M1 macrophage phenotype, a decrease in T beta R-I/Smad2/3 activation, and in the Smad4 expression at 3 days, while akirin1 expression increased at 10 days in muscles from beta 2KO mice when compared to those from wild type. Conclusions: Our results suggest that the beta 2-adrenoceptor contributes to the regulation of the initial phases of muscle regeneration, especially in the control of macrophage recruitment in regenerating muscle through activation of TbR-I/Smad2/3 and reduction in akirin1 expression. These findings have implications for the future development of better therapeutic approaches to prevent or treat muscle injuries. (AU)

• Processo FAPESP: 12/21238-2 - Plasticidade do músculo esquelético após lesão: papel do receptor beta2-adrenérgico
• Beneficiário: Elen Haruka Miyabara
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/53528-7 - Plasticidade muscular esquelética após injúria e atrofia: influência das proteínas de choque térmico
• Beneficiário: Elen Haruka Miyabara
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/54240-7 - Papel do adrenocpetor beta 2 na regeneracao muscular esqueletica
• Beneficiário: Meiricris Tomaz da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 08/57256-9 - Papel do agonista beta 2-adrenergico (formoterol) na minimizacao do deficit regenarativo de musculos esqueleticos de ratos idosos
• Beneficiário: Elen Haruka Miyabara
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/12593-0 - Efeito da estimulação beta2-adrenérgica na minimização do déficit regenerativo de músculos esqueléticos de ratos idosos.
• Beneficiário: Lucila Hernandes da Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado