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Identification and caracterization of mechanisms involved in skeletal muscle mass control and regeneration

Abstract

This project contains a series of proposals aiming to deepen the knowledge on cellular and molecular mechanisms that control skeletal muscle mass and regeneration. This knowledge is key to the future development of therapeutic strategies that can improve skeletal muscle viability, consequently increasing quality of life. Noteworthy, there are a number of key clinical conditions involving significant loss of skeletal muscle such as peripheral nerve injury, long term limb immobilisation, ageing and diseases with severe metabolic stress as AIDS, sepsis and cancer. In addition, maintanance of skeletal muscle mass is essencial for basic homeostasis, including daily motor activities (posture and movement), thermogenesis, energetic balance and immune response. Regenerative capacity is also a key adaptive feature of skeletal muscle, not only to repair large injuries, but also to repair micro injuries that occur by the ordinary mechanical demand. Indeed the slow and progressive loss of skeletal muscle mass in ageing is, among other factors, caused by lack of proper regeneration. Therefore, in certain conditions, skeletal muscle mass loss and regeneration are complementary and inter related processes. Subprojects 1-3 are directly related to understanding of underlying mechanisms. Another strategy will be to use an anti-atrophic agent (leucine) and another atrophic (Thyroid hormone) as models to identify possible target molecules/pathways (sub projects 4, 5, 6, 7 and 8). (AU)

Articles published in other media outlets (4 total):
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UOL: Uso de microRNAs pode combater desgastes dos músculos (15/Oct/2019)
Brasil CT&I: Pesquisadores desenvolvem técnica que promove ganho de força e previne atrofia muscular (16/Oct/2019)
Jornal da USP online: Uso de microRNAs pode combater desgastes dos músculos (14/Oct/2019)
APM- Associação Paulista de Medicina: Cientista brasileiro pesquisa terapia genética para ganhar massa muscular (10/Sep/2019)

Scientific publications (7)
(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)
LABEIT, SIEGFRIED; HIRNER, STEPHANIE; BOGOMOLOVAS, JULIJUS; CRUZ, ANDRE; MYRZABEKOVA, MOLDIR; MORISCOT, ANSELMO; BOWEN, THOMAS SCOTT; ADAMS, VOLKER. Regulation of Glucose Metabolism by MuRF1 and Treatment of Myopathy in Diabetic Mice with Small Molecules Targeting MuRF1. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 4 FEB 2021. Web of Science Citations: 0.
ALVES, PAULA K. N.; CRUZ, ANDRE; SILVA, WILLIAM J.; LABEIT, SIEGFRIED; MORISCOT, ANSELMO S. Leucine Supplementation Decreases HDAC4 Expression and Nuclear Localization in Skeletal Muscle Fiber of Rats Submitted to Hindlimb Immobilization. CELLS, v. 9, n. 12 DEC 2020. Web of Science Citations: 0.
CRUZ, ANDRE; FERIAN, ANDREA; ALVES, PAULA K. N.; SILVA, WILLIAM JOSE; BENTO, MIRELLA RIBEIRO; GASCH, ALEXANDER; LABEIT, SIEGFRIED; MORISCOT, ANSELMO SIGARI. Skeletal Muscle Anti-Atrophic Effects of Leucine Involve Myostatin Inhibition. DNA AND CELL BIOLOGY, v. 39, n. 12 NOV 2020. Web of Science Citations: 0.
ADAMS, VOLKER; GUSSEN, VICTORIA; ZOZULYA, SERGEY; CRUZ, ANDRE; MORISCOT, ANSELMO; LINKE, AXEL; LABEIT, SIEGFRIED. Small-Molecule Chemical Knockdown of MuRF1 in Melanoma Bearing Mice Attenuates Tumor Cachexia Associated Myopathy. CELLS, v. 9, n. 10 OCT 2020. Web of Science Citations: 0.
J.G. SILVESTRE; I.L. BAPTISTA; W.J. SILVA; A. CRUZ; M.T. SILVA; E.H. MIYABARA; S. LABEIT; A.S. MORISCOT. The E3 ligase MuRF2 plays a key role in the functional capacity of skeletal muscle fibroblasts. Brazilian Journal of Medical and Biological Research, v. 52, n. 9, p. -, 2019. Web of Science Citations: 0.
RAMOS, G. V.; CRUZ, A.; SILVA, W. J.; ROZANSKI, A.; BAPTISTA, I. L.; SILVESTRE, J. G.; MORISCOT, A. S. Thyroid hormone upregulates MDM2 in rat type I fibre: Implications for skeletal muscle mass regulation. ACTA PHYSIOLOGICA, v. 222, n. 4 APR 2018. Web of Science Citations: 1.
BAPTISTA, IGOR L.; SILVESTRE, JOAO G.; SILVA, WILLIAM J.; LABEIT, SIEGFRIED; MORISCOT, ANSELMO S. FoxO3a suppression and VPS34 activity are essential to anti-atrophic effects of leucine in skeletal muscle. Cell and Tissue Research, v. 369, n. 2, p. 381-394, AUG 2017. Web of Science Citations: 5.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
Filed patent(s) as a result of this research project

Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação BR1020180677020 - Universidade de São Paulo (USP) . Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação - September 2018, 03