The role of non-canonical Stat3/TGF-B1 pathway in the satellite cells fate in mdx mice

• Grant number: 15/26767-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 15, 2016
• End date: May 14, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Luiz Augusto Buoro Perandini
• Supervisor: Thomas Rando
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Stanford University, United States
• Associated to the scholarship: 14/21005-3 - Skeletal muscle repair in response to eccentric exercise-induced muscle damage: STAT3 signaling pathway on proliferation and differentiation of satellite cells, BP.PD

Abstract

The skeletal muscle has the capacity to regenerate in response to tissue damage which has been associated with the activation of the satellite cells. In patients with muscle dystrophies and aged population, there is a reduction in this capacity which seems to be related to a change in the satellite cells fate. It is known that satellite cells fate from mdx (an experimental model resembling the Duchenne Disease) and aged mice are changed to a pro-fibrotic pattern. Moreover, this change was related to the activation of Wnt/TGF-²2 signaling pathway. Another signaling pathway which is associated to increase in fibrosis is the non-canonical Stat3/TGF-²1; however, to date it was not investigated if this pathway could be involved in the change of satellite cells fate in mdx mice. Also, a single bout and chronic eccentric exercise seem to increase Stat3 and TGF-²1, therefore, it is important to know if this type of exercise is detrimental than beneficial. Thus, the aims of this study are to investigate if the non-canonical Stat3/TGF-²1 signaling pathway is related to the change of the satellite cells fate in mdx mice, and to explore whether eccentric exercise training could increase the activation of this non-canonical pathway, thereby worsening the skeletal muscle fibrosis and function. Several mice strains, such as Myf5CreER/WT, Stat3flox/flox and Myf5CreER, R26RYFP and mdx5Cv will be used to induce fibrosis in the skeletal muscle following the protocol established by Professor Rando's lab. Moreover, in vitro studies with primary satellite cells will be performed in order to meticulously assess the mechanisms related to the change in the satellite cells fate and effects of the chronic eccentric exercise training. We expect to unravel new mechanisms involved in the fibrosis during muscle dystrophy that could imply in a better outcome for patients in the future.

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)

BRETT, JAMIE O.; ARJONA, MARINA; IKEDA, MIKA; QUARTA, MARCO; DE MORREE, ANTOINE; EGNER, INGRID M.; PERANDINI, LUIZ A.; ISHAK, HEATHER D.; GOSHAYESHI, ARMON; BENJAMIN, DANIEL I.; et al. Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1. NATURE METABOLISM, v. 2, n. 4, p. 307+, APR 2020. (15/26767-1)