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Content archived on 2024-06-18

Molecular mechanisms involved in skeletal muscle repair and muscular dystrophy

Objective

The objective of this proposal is to define the role of histone deacetylase 4 (HDAC4) and myocyte enhancer factor 2 (MEF2) in muscle regeneration and dystrophy. In response to injury, skeletal muscle activates orchestrated molecular mechanisms to restore muscle architecture and functionality. Our preliminary data showed that skeletal muscle from mice lacking HDAC4, an inhibitor of the myogenic factor MEF2, regenerates better than that of control mice following injury. MEF2 activity is triggered in healthy myofibers surrounding the injured area, suggesting a potential role of MEF2 in paracrine regulation of adult muscle regeneration. We demonstrated that MEF2 controls the expression of caveolin3, an inhibitor of myostatin, a negative regulator of muscle mass. In this proposal, we plan to define the role of HDAC4 in muscle regeneration by identifying the targets responsible for the improved regeneration observed in HDAC4 null mice. We intend to study how HDAC4 regulates satellite cell proliferation and differentiation. In order to identify secreted factors that may contribute to the improved regeneration in HDAC4 null mice, we plan to perform a proteomic analysis on secretomes from HDAC4 null and control myofibers. Muscular dystrophies are a hereditary myopathies characterized by progressive muscle degeneration and weakness. Promoting muscle repair has been shown to be therapeutically beneficial for muscular dystrophy. We intend to study the role of HDAC4 in muscular dystrophy by characterizing mdx mice lacking HDAC4 in skeletal muscle. We will define MEF2 activity and we will determine target genes controlled by HDAC4 in muscular dystrophy. By delineating the role of HDAC4 in skeletal muscle regeneration and dystrophy, we will provide an experimental framework for developing new drugs to improve muscle repair and ameliorate muscular dystrophy.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2011-CIG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
EU contribution
€ 100 000,00
Address
Piazzale Aldo Moro 5
00185 Roma
Italy

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Region
Centro (IT) Lazio Roma
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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