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Role of macrophage subtypes in secretion of growth factors and pathway activation associated with muscle hypertrophy in PPAR-± knockout mice after exercise induced muscle damage

Grant number: 19/05797-0
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2020
Effective date (End): May 31, 2024
Field of knowledge:Health Sciences - Physical Education
Principal Investigator:Ronaldo Vagner Thomatieli dos Santos
Grantee:Andre Luis Araujo Minari
Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil


Different from the processes of severe muscle injury few studies have examined the participation of Mac after low-intensity muscle injuries such as EIMD (exercise-induced muscle damage). In the triceps muscle of mice, we identified that the LIEF was responsible for elevating predominantly Ly6C + Mac, being these subsets one of the main responsible for the secretion of substances related to muscle hypertrophy processes. In this sense, this study aims to: Evaluate the contribution of PPAR-± on the activation of pathways associated with muscle hypertrophy and the secretion of growth factors by MAC after the downhill protocol of physical exercise. For this, two type of mice, wild PPAR-± (+ / +) and KO animals (KNOCKOUT) for PPAR-± (PPAR-± (- / -)) will be used in 3 sequential experiments. Experiment 1 and 2, in vivo, where we will evaluate the participation of Macs and PPAR-± in muscle injury after EIMD, such as the MaC subtypes, proteins (PPAR-±, PI3K, AKT / mTOR) and growth factors (IGF-1, TGF-² and GDF-3), involved with muscle hypertrophy processes. In the experiment-3,we will perform experiments in vitro evidencing the production of cytokines and growth factors stimulated in Mac by fenofibrates. For experiment 1 and 2, the EIMD protocol use will be the downhill protocol (eccentric EF in slope -16 °, with the session consisting of 18 shots of 5 minutes at the average velocity of 16m / min, interval for 2 min. rest). After the EIMD protocol, the animals will be euthanized before (CTRL), 48, 72 and 96h after. For the in vitro experiments, the cells will be extracted from the bone marrow and differentiate into Macs. For the statistical analysis, the data will be submit to the normality and homogeneity test, thus determining the most appropriate statistical test taking into account the experimental design. Results: will be demonstrate in mean and standard deviation (D.P).

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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)
ARAUJO MINARI, ANDRE LUIS; THOMATIELI-SANTOS, V, RONALDO. From skeletal muscle damage and regeneration to the hypertrophy induced by exercise: what is the role of different macrophage subsets?. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 322, n. 1, p. R41-R54, . (19/05797-0, 18/19678-0)

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