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Zawartość zarchiwizowana w dniu 2024-06-18

Role of the transcription factor Nfix in muscle regeneration and muscular dystrophies

Cel

I will study the role of the transcription factor Nfix, in post-natal skeletal muscle growth and regeneration, and in the pathogenesis of muscular dystrophies. I have recently demonstrated the role of the transcription factor Nuclear Factor IX, Nfix, in driving the transcriptional switch from embryonic to fetal myogenesis, characterized by a switch from slow to fast twitching and more mature fibers. Current data show that Nfix is also strongly expressed in satellite cells (SCs), the muscle adult stem cells responsible for post-natal muscle growth and regeneration. Therefore, I will investigate: 1. The gene expression profile of the muscle specific Nfix null SCs in vitro in comparison with wt SCs. 2. The ability of Nfix deficient SCs to repair muscle damage in comparison with wt SCs. Moreover, I will study the possible use of Nfix in muscular dystrophies. Muscular dystrophies are characterized by primary wasting of skeletal muscle and currently lack a therapy. Among the different approaches, many efforts are directed to induce hypertrophy in dystrophic to counteract progressive degeneration. This is achieved by enhancing regeneration at the expense of the satellite cell pool. Interestingly, fast muscle fibers are preferentially affected in different muscular dystrophies. As Nfix regulates slow myosin expression, I propose that a slower twitching muscle may escape muscle degeneration in a dystrophic mouse model. In this perspective, the possible interference of Nfix with the pathogenesis of muscular dystrophy will be studied by crossing muscle-specific Nfix null mice alpha sarcoglycan null mice ( a model for Limb Girdle 2D muscular dystrophy) (Aim 3). The results of this study will have important implications for the understanding of the mechanisms regulating post-natal muscle growth and regeneration and potentially as a novel therapy for muscular dystrophy.

Zaproszenie do składania wniosków

ERC-2011-StG_20101109
Zobacz inne projekty w ramach tego zaproszenia

System finansowania

ERC-SG - ERC Starting Grant

Instytucja przyjmująca

UNIVERSITA DEGLI STUDI DI MILANO
Wkład UE
€ 1 386 945,00
Adres
Via Festa Del Perdono 7
20122 Milano
Włochy

Zobacz na mapie

Region
Nord-Ovest Lombardia Milano
Rodzaj działalności
Higher or Secondary Education Establishments
Kierownik naukowy
Graziella Messina (Dr.)
Linki
Koszt całkowity
Brak danych

Beneficjenci (1)