Skeletal muscle repair in response to eccentric exercise-induced muscle damage: STAT3 signaling pathway on proliferation and differentiation of satellite cells

• Grant number: 14/21005-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2015
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Luiz Augusto Buoro Perandini
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches, AP.TEM
• Associated scholarship(s): 15/26767-1 - The role of non-canonical Stat3/TGF-B1 pathway in the satellite cells fate in mdx mice, BE.EP.PD

Abstract

The skeletal muscle regeneration process occurs in response to muscle fibers damage. The main mechanisms of this process had been studied since the reduction of regeneration capacity has been associated com frailty and mortality. Therefore, the aim of the present study will be to assess the role of Stat3 in the proliferation and differentiation of satellite cells during muscle regeneration process in response to muscle damage induced by eccentric exercise. C57Bl/6 as a wild type (WT), Myf5-Cre/Stat3flox/flox, and Myf5CreER/Stat3flox/flox mice of 6 to 8 weeks of age will be used in the present study. Initially, mice will perform a single bout of eccentric exercise by 60 minutes, 17 m/min, -15% of grade to determine the time-course of the satellite cells proliferation and differentiation, and muscle regeneration markers. All these measures will be assessed in the extensor digitorum longus (EDL) and gastrocnemius (GC) muscles of mice after 4 hours, 1, 3, 5, and 10 days of recovery. The euthanized of mice after eccentric exercise will be determined based on time-course assessment of each muscle. In order to identify the role of Stat3 in muscle regeneration in response to eccentric exercise, Myf5-Cre/Stat3flox/flox mice will perform a single bout of eccentric exercise and markers of satellite cells proliferation and differentiation will be assessed. The assessment of individually role of Stat3 in satellite cells proliferation and differentiation will be obtained after tamoxifen injection in the Myf5-CreER/Stat3flox/flox after eccentric exercise. Similarly, skeletal muscle precursors cells of WT and Myf5-Cre/Stat3flox/flox mice will be transplanted in the same time point after eccentric exercise. Finally, both mice will be submitted to chronic eccentric exercise to assess if acute response to eccentric exercise will be maintained after consecutive stimuli. Based on these experiments, we expected that muscle regeneration will be impaired in mice with Stat3 ablation in satellite cells and this impairment will arise from satellite cells proliferation failure. These results will help to understand the satellite cells signaling pathway during muscle regeneration process, which will allow new approaches to minimize deleterious effects caused by reduction in the muscle regeneration capacity. (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)

PERANDINI, LUIZ AUGUSTO; CHIMIN, PATRICIA; LUTKEMEYER, DIEGO DA SILVA; SARAIVA CAMARA, NIELS OLSEN. Chronic inflammation in skeletal muscle impairs satellite cells function during regeneration: can physical exercise restore the satellite cell niche?. FEBS Journal, v. 285, n. 11, p. 1973-1984, JUN 2018. (12/02270-2, 14/21005-3)