Skeletal muscle regeneration in mice with Marfan Syndrome: study of the regenerative potential of satellite cells

• Grant number: 14/13874-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): January 01, 2015
• Effective date (End): December 31, 2018
• Field of knowledge: Biological Sciences - Morphology - Histology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Elen Haruka Miyabara
• Grantee: Meiricris Tomaz da Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 17/14115-5 - Study of the satellite cell regenerative capacity in mice with Marfan syndrome, BE.EP.PD

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 extracellular matrix protein fibrillin-1 found in different organs and tissues. Although poorly studied, muscle abnormalities such as hypoplasia and hypotonia, decreased strength and susceptibility to fatigue are frequent in this syndrome. Histological analyses of skeletal muscles from fibrillin-1-deficient mice and from patients with SMF showed a decrease in the number and size of myofibers, combined with fibrosis, deposition of adipose tissue and myofiber splitting. Although a study 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. In addition, the investigation of possible therapeutic strategies to improve the muscle regenerative potential of these individuals has been poorly explored. The purpose of this study is to contribute to a better understanding 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 adult 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)

PEREIRA, MARCELO G.; SILVA, MEIRICRIS T.; DA CUNHA, FERNANDA M.; MORISCOT, ANSELMO S.; AOKI, MARCELO S.; MIYABARA, ELEN H.. Leucine supplementation improves regeneration of skeletal muscles from old rats. Experimental Gerontology, v. 72, p. 269-277, DEC 2015. (12/15276-9, 12/50500-7, 14/13874-1, 13/07937-8)

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)