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Skeletal muscle plasticity after injury: role of beta2-adrenoceptor

Grant number: 12/21238-2
Support type:Regular Research Grants
Duration: April 01, 2013 - March 31, 2015
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Elen Haruka Miyabara
Grantee:Elen Haruka Miyabara
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Skeletal muscle regeneration is essential for muscle integrity, however the intracelular mechanism involved in this process are still not totally understood. A possible regulator of the muscle regenerative process could be the beta2 adrenoceptor, because it has been described that synthetic beta2-adrenoceptor agonists are able to maximize the recovery of the size of regenerating myofibers, leading to the improvement of the structure and consequent function of skeletal muscles from young animals. In addition, studies have shown that the adrenoceptor beta2-agonist clembuterol is able to anticipate the proliferation of satellite cells in transplanted young muscles. Recently, our group has also demonstrated that the beta2-adrenoceptor agonist formoterol improves structural and functional regerative capacity of skeletal muscles from old rats (Conte, T. C. et al., 2012).Therefore, it is possible that the beta2-adrenoceptor agonist might have an important role in skeletal muscle regeneration. Thus, we decided to study the role of beta2-adrenoceptor agonist in muscle regeneration using beta2-adrenoceptor knockout mice. The following aspects will be analyzed: macroscopic (muscle and body weight), histological (toluidine blue staining), immunohistochemical (detection of macrophages, activating/proliferating satellite cells and differentiating muscle cells in the muscle tissue from the knockout mice), cellular (using culture of satellite cells isolated by fluorescence activated cell sorter - FACS, in order to analyze cell proliferation and differentiation in vitro), molecular (measurement of the amount of AMPc produced in muscle tissue, expression detection of proteins relevant to muscle regeneration such as myostatin, akirin-1 and proteins from the PI3K/ AKT/mTOR pathway) and functional (analysis of muscle contraction) in different stages of regeneration (1, 3, 10 and 21 days postinjury) of soleus muscles. The role of beta2-adrenoceptor in satellite cell proliferation and subsequente differentiation in vitro will also be performed by the post-transcriptional silencing of the beta2-adrenoceptor gene through satellite cell transfection (isolated from hindlimbs of wild type mice) with RNA interference. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NASCIMENTO, T. L.; CONTE, T. C.; RISSATO, T. S.; LUNA, M. S.; SOARES, A. G.; MORISCOT, A. S.; YAMANOUYE, N.; MIYABARA, E. H. Radicicol enhances the regeneration of skeletal muscle injured by crotoxin via decrease of NF-kB activation. Toxicon, v. 167, p. 6-9, SEP 2019. Web of Science Citations: 0.
SILVA, MEIRICRIS T.; NASCIMENTO, TABATA L.; PEREIRA, MARCELO G.; SIQUEIRA, ADRIANE S.; BRUM, PATRICIA C.; JAEGER, RUY G.; MIYABARA, ELEN H. beta 2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9. Cell and Tissue Research, v. 365, n. 1, p. 173-186, JUL 2016. Web of Science Citations: 0.
SILVA, M. T.; WENSING, L. A.; BRUM, P. C.; CAMARA, N. O.; MIYABARA, E. H. Impaired structural and functional regeneration of skeletal muscles from beta 2-adrenoceptor knockout mice. ACTA PHYSIOLOGICA, v. 211, n. 4, p. 617-633, AUG 2014. Web of Science Citations: 11.

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