Publication:
PITX2 Enhances the Regenerative Potential of Dystrophic Skeletal Muscle Stem Cells.

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Date

2018

Authors

Vallejo, Daniel
Hernández-Torres, Francisco
Lozano-Velasco, Estefanía
Rodriguez-Outeiriño, Lara
Carvajal, Alejandra
Creus, Carlota
Franco, Diego
Aránega, Amelia Eva

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Abstract

Duchenne muscular dystrophy (DMD), one of the most lethal genetic disorders, involves progressive muscle degeneration resulting from the absence of DYSTROPHIN. Lack of DYSTROPHIN expression in DMD has critical consequences in muscle satellite stem cells including a reduced capacity to generate myogenic precursors. Here, we demonstrate that the c-isoform of PITX2 transcription factor modifies the myogenic potential of dystrophic-deficient satellite cells. We further show that PITX2c enhances the regenerative capability of mouse DYSTROPHIN-deficient satellite cells by increasing cell proliferation and the number of myogenic committed cells, but importantly also increasing dystrophin-positive (revertant) myofibers by regulating miR-31. These PITX2-mediated effects finally lead to improved muscle function in dystrophic (DMD/mdx) mice. Our studies reveal a critical role for PITX2 in skeletal muscle repair and may help to develop therapeutic strategies for muscular disorders.

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MeSH Terms

Animals
Cell Differentiation
Down-Regulation
Dystrophin
Homeodomain Proteins
Mice, Inbred C57BL
Mice, Inbred mdx
MicroRNAs
Models, Biological
Muscle Development
Muscular Dystrophy, Duchenne
Myoblasts
Regeneration
Satellite Cells, Skeletal Muscle
Transcription Factors

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Keywords

PITX2, miR-31, muscle stem cells, muscular dystrophy

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