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

• Grant number: 15/04090-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: July 01, 2015
• End date: September 30, 2021
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Anselmo Sigari Moriscot
• Grantee: Anselmo Sigari Moriscot
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Asa Birgitta Gustafsson ; Chao Yun Irene Yan ; Elen Haruka Miyabara
• Associated scholarship(s): 21/05827-7 - Effect of leucine on the expression of miR-299a and HDAC4 in the skeletal muscle of rats submitted to hind limb immobilization: implications for the control of muscle mass, BP.DD; 19/08996-4 - Effects of miR-29c on skeletal muscle plasticity: implications for the control of muscle mass, BP.PD; 18/24418-8 - Tribbles 3 role in skeletal muscle regeneration, BP.DD; + associated scholarships 18/24419-4 - Effect of leucine on the expression of miR-299A and HDAC4 in the skeletal muscle of rats submitted to immobilization: implications for the control of muscle mass, BP.DD; 18/21187-5 - Identification of leucine responsive genes in immobilized skeletal muscle: a combined approach involving mRNA and microRNA sequencing, BP.TT; 17/09398-8 - Interplay betweeen myostatin and mTORC1 pathways in skeletal muscle: implications for a thyroid hormone biological action, BP.DD; 16/12941-2 - Identification and characterization of leucine responsive mRNAs in skeletal muscle of rats subjected to immobilization with large-scale sequencing, BP.PD - associated scholarships

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)

Scientific publications

(12)

(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)

NASCIMENTO ALVES, PAULA KETILLY; CRUZ, ANDRE; SILVA, WILLIAM J.; LABEIT, SIEGFRIED; MORISCOT, ANSELMO SIGARI. miR-29c Increases Protein Synthesis in Skeletal Muscle Independently of AKT/mTOR. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 13, p. 11-pg., 2022-07-01. (21/05827-7, 19/08996-4, 18/24419-4, 15/04090-0, 17/09398-8, 21/03066-9)

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. (12/13071-0, 17/09398-8, 12/13315-7, 12/22488-2, 15/04090-0)

ALVES, PAULA K. N.; CRUZ, ANDRE; ADAMS, VOLKER; MORISCOT, ANSELMO S.; LABEIT, SIEGFRIED. Small-molecule mediated MuRF1 inhibition protects from doxorubicin-induced cardiac atrophy and contractile dysfunction. European Journal of Pharmacology, v. 984, p. 9-pg., 2024-10-07. (18/24419-4, 21/03066-9, 17/09398-8, 19/08996-4, 21/05827-7, 15/04090-0)

NASCIMENTO ALVES, PAULA KETILLY; SILVESTRE, JOAO G.; DAMASCENA SOUGEY, WENDDY WYLLIE; CRUZ, ANDRE; MORISCOT, ANSELMO SIGARI. Improved Electrical Stimulation-Based Exercise Model to Induce Mice Tibialis Anterior Muscle Hypertrophy and Function. APPLIED SCIENCES-BASEL, v. 12, n. 15, p. 14-pg., 2022-08-01. (18/24418-8, 16/12941-2, 21/05827-7, 18/24419-4, 15/04090-0, 17/09398-8, 21/03066-9, 17/26819-7)

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, 2019-08-29. (12/13315-7, 16/12941-2, 15/04090-0)

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. (15/04090-0)

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. (15/04090-0, 19/06819-8)

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. (19/06819-8, 15/04090-0)

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. (12/22488-2, 13/19387-2, 15/04090-0, 17/09398-8, 18/24419-4)

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. (15/04090-0, 18/24419-4, 17/09398-8)

GRACA ZUANAZZI, FLAVIA APARECIDA; BENTO, MIRELLA; SILVESTRE, JOAO GUILHERME; MORISCOT, ANSELMO SIGARI. KLF15 is modulated by leucine in skeletal muscle submitted to immobilization in rats. FASEB JOURNAL, v. 31, p. 1-pg., 2017-04-01. (15/04090-0)

SILVESTRE, JOAO GUILHERME; CRUZ, ANDRE; BENTO, MIRELLA RIBEIRO; GRACA, FLAVIA APARECIDA; MORISCOT, ANSELMO SIGARI. Identification of mRNAs Responsive to Leucine in Skeletal Muscle of Rats-A Deep-Sequencing Approach. FASEB JOURNAL, v. 31, p. 2-pg., 2017-04-01. (15/04090-0, 16/12941-2)

Filed patent(s) as a result of this research project