Study of the regenerative capacity of sattelite cells from different dystrophic mice models

• Grant number: 09/11515-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2009
• End date: January 31, 2013
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariz Vainzof
• Grantee: Paula Cristina Gorgueira Onofre Oliveira
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 98/14254-2 - The Human Genome Research Center, AP.CEPID

Abstract

The muscular dystrophies are a heterogeneous group of genetic diseases characterized by progressive and irreversible degeneration of skeletal muscles. Muscle weakness is the consequence of an imbalance between successive cycles of degeneration and regeneration, with further replacement of the degraded muscle fibers by adipose and connective tissues. Several factors are involved these processes and the respective functional pathways are still not well known. Myf5, MyoD, Myf6 and myogenin are important factors responsible for the myogenesis and regeneration in the muscle. One important marker for the degeneration is TGF²-1, which is an inflammatory cytokine with a possible role in the stimulation of fibrosis in the dystrophic muscle through the activation of genes related to the expression of collagen. In our previous research we quantified the expression of genes involved in degeneration and regeneration pathways in the dystrophic models mdx, SJL/J, Lama2dy-2J/J and Largemyd, and correlated these data with muscle histopathological pattern of each model. The result suggested that TGF²-1 gene is activated in the dystrophic process in all the stages of degeneration while the activation of the expression of the pro-collagen gene possibly occurs in earliest stages of this process. According to these differences in induction of proliferation of satellite cells, but no changes in the stimulus to differentiation, we suggest that the cascade of degeneration of each pathophysiological pathway may act in a different way in the activation of regeneration. To further investigate these aspects, the objectives of this project are to assess the possible differences in mechanisms of activation and activity of the satellite cells in dystrophic muscle of murine models Largemyd and Lama2dy-2J / J, which have very similar pattern of degeneration, but with differences in the pattern of regeneration. The satellite cells will be isolated from affected muscles of mice and characterized as the expression of myogenic factors, markers of pluripotent stem cells, capacity of proliferation and differentiation in vitro. If we found some subpopulations they will be isolated and cloned and we will study the profile of gene expression through microarray of expression, to verify differences in the metabolic activation of several cascades.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

OLIVEIRA, Paula Cristina Gorgueira Onofre. Characterization of satellite-cells gene expression profile from dystrophic mice carrying different molecular defects. 2013. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.