Skeletal muscle mass control by microRNA-29c manipulation: a molecular intervention approach

• Grant number: 21/03066-9
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: February 29, 2024
• 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 scholarship(s): 22/10501-6 - Modulation of microRNA-29c to control skeletal muscle mass,, BP.TT; 22/11907-6 - Modulation of microRNA-29c to control skeletal muscle mass, BP.TT

Abstract

Skeletal muscle dysfunction results in inadequate control of homeostasis and particularly a significant skeletal muscle loss (sarcopenia) has a substantial negative impact in the senile fragility syndrome onset in aging. This syndrome is characterized by an increased mortality due an individual's lower ability to maintain vital functions and typical immunological response. Furthermore, we can observe marked skeletal muscle loss after joint injuries, for instance, anterior cruciate ligament rupture. After the ligament injury, a severe skeletal muscle wasting of the stabilizing musculature leads to a lengthy rehabilitation process, even after the ligament reconstruction. Both examples endorse the need to developing therapeutics that enable the maintenance of muscle mass and function, which is the context of this proposal. In this sense, we demonstrated previously that miR-29c hyperexpression induced a 40% increase in skeletal muscle mass and force, regardless of the mechanical load. Also, preliminary data (shown in this proposal) indicates that this microRNA may also have an anti-atrophic action. Herein, we will address miR-29c ergogenic effects upon skeletal muscle in atrophy (denervation, glucocorticoids, and cancer cachexia) and hypertrophy models (electrical stimulation). Next, functional (muscle strength), morphometric (muscle mass, cross-sectional area of different types of muscle fibers), and molecular (gene expression of pathways linked to atrophy and hypertrophy) aspects of the skeletal muscle will be evaluated. In addition, we will carry out a prospective experiment to identify miR-29c responsive-mRNAs, microRNAs, and long non-coding RNAs regulated by these different conditions. Together, our results and literature content support miR-29c therapeutic potential. Furthermore, understanding its possible interaction with the mechanical stress imposed by muscle contraction may open the possibility of future approaches involving clinical conditions in which it is desired to contain the loss or optimize muscle mass gain. (AU)

Scientific publications

(4)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

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)

RIBEIRO, FERNANDO; ALVES, PAULA K. N.; BECHARA, LUIZ R. G.; FERREIRA, JULIO C. B.; LABEIT, SIEGFRIED; MORISCOT, ANSELMO S.. Small-Molecule Inhibition of MuRF1 Prevents Early Disuse-Induced Diaphragmatic Dysfunction and Atrophy. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 4, p. 17-pg., 2023-02-01. (20/04607-0, 21/03066-9)

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; 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)