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Survey for microRNAs targeting MuRF1 and MuRF2 in skeletal muscle regeneration and mass control

Grant number: 15/24716-0
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): March 01, 2016
Effective date (End): February 28, 2017
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Anselmo Sigari Moriscot
Grantee:William Jose da Silva
Supervisor abroad: Da-Zhi Wang
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Harvard University, Boston, United States  
Associated to the scholarship:12/22488-2 - Expression of microRNAs in the skeletal muscle plasticity: the possible interrelationships with MuRFs effect in the regenerative process, BP.DD

Abstract

Skeletal muscle is highly specialized in the production of force and motion, and can adapt to different stimulus such as mechanical demands increase, hormonal status and injury. The injury leads to regenerative response that targets the tissue repair. The regeneration process is extremely important for maintaining functional quality, not only skeletal muscle tissue after acute injury, but also to deal with micro-lesions that occur in daily life activities. Thus the knowledge of the cellular/molecular mechanisms involved in the regenerative process is also important. Findings in another ongoing project in our laboratory show that MuRF1 and MuRF2 play an important role during muscle regeneration, therefore going beyond their well-known roles as E3 ligases in muscle atrophy process. We know that these two MuRFs are strongly induced during regeneration by a still unknown mechanism. Therefore, our hypothesis is that certain miRNAs (microRNAs or miRs) are capable of inhibiting MuRF1 and MuRF2 after injury and that these miRNAs are suppressed, allowing overexpression of MuRFs. In our preliminary results we seek in literature and in silico miRNAs potentially involved in the inhibition of MuRFs in the context of skeletal muscle regeneration and we selected miR-29c and miR-101a target MuRF1 and miR-133a/b target MuRF2, after we validate this miRNAs in vitro by gene Reporter assay. In this study, with the expertise of Dr. Wang, we will development AAV base vector to modulated expression of miRNAs and MuRFs in mice injured with cardiotoxin in order to understand their impact on the regenerative process. (AU)