Regenerative response of skeletal muscles from mice with Marfan Syndrome

• Grant number: 14/23391-8
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2015 - September 30, 2017
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Elen Haruka Miyabara
• Grantee: Elen Haruka Miyabara
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Marfan syndrome (SMF) is an autosomal-dominant systemic disorder of connective tissue, caused by a mutation of fibrillin-1 gene, resulting in changes in the protein fibrillin-1, the major component of microfibrils of the extracellular matrix, present in elastic and non-elastic connective tissues. Although poorly studied, alterations in skeletal muscles from fibrillin-1-deficient mice and from patients with SMF are frequent, such as a decrease in the number and size of myofibers, fibrosis, deposition of adipose tissue, myofiber splitting, hypotonia, decreased strength and susceptibility to fatigue. Although a work has reported that there is a deficit in skeletal muscle regeneration in animals with a mutation of fibrillin-1, the cellular and molecular mechanisms that characterize the impaired muscle regenerative response in these individuals have not been systemically investigated yet. Furthermore, the investigation of possible therapeutic strategies to improve the muscle regenerative potential of these individuals has been poorly explored. The aim of this study is to contribute to a better understanding of the morphological, cellular, molecular and functional aspects of the muscle regenerative process in individuals with SMF, specially the function of satellite cells by using the genetic model that is based on the Cre/loxP system to genetically label satellite cells from animals with SMF (please, verify details in the project); as well as to test possible therapeutic strategies [pharmacological treatment with Ang-(1-7) and transplantation of satellite cells overexpressing the heat shock protein 70 kDa; HSP70] in order to improve the muscle regenerative potential of these individuals. (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)

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. (14/13874-1, 14/23391-8, 13/04783-0, 12/21238-2)

NASCIMENTO, TABATA L.; SILVA, MEIRICRIS T.; MIYABARA, ELEN H.. BGP-15 improves contractile function of regenerating soleus muscle. JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY, v. 39, n. 1-2, p. 25-34, APR 2018. (14/13874-1, 14/23391-8, 13/04783-0)