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Muscular dystrophy protection: microRNAs approach and pharmacological therapy

Grant number: 13/10633-0
Support type:Regular Research Grants
Duration: October 01, 2013 - March 31, 2016
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Renato Ferretti
Grantee:Renato Ferretti
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

In Duchenne muscular dystrophy (DMD) and in the mdx mice, the experimental model of DMD, the lack of dystrophin leads to muscle necrosis and progressive cardiorespiratory failure. The absence of dystrophin leads to a decrease in expression of dystrophin-glycoprotein complex (DGC) and loss of homeostasis of calcium (Ca2+), resulting in myonecrosis. MicroRNAs (miRs), non-coding RNAs, appear to coordinate the signaling pathways that predispose to muscle fiber necrosis. Studies showed that the intrinsic laryngeal muscles (ILM) are protected from myonecrosis, probably because they had normal levels of components of the DGC and better ability to regulate calcium. In the present study, we will investigate whether the miRs are involved in protecting against myonecrosis in mdx mice. We will carry out a comparative study of the pathways that regulate the expression of components that help stabilizes the sarcolemma and are involved in Ca2+ homeostasis in dystrophic spared and affected muscles. Additionally, we will evaluate the effect of therapy with eicosapentaenoic acid (EPA) in the expression of these miRs and their correlation with protection against myonecrosis in dystrophinopathies. This project will offer new mechanistic insights into the pathophysiology of dystrophinopathies opening new perspectives of therapies for DMD. (AU)

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)
FERRETTI, RENATO; MARQUES, MARIA JULIA; KHURANA, TEJVIR S.; NETO, HUMBERTO SANTO. Expression of calcium-buffering proteins in rat intrinsic laryngeal muscles. PHYSIOLOGICAL REPORTS, v. 3, n. 6 JUN 2015. Web of Science Citations: 1.

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