ABL1 loss of function in adult myoblasts: Effects on differentiation and muscle regeneration

Fabian J. Montecino; Alvarez, Alejandra; OlguÍn, Hugo CÉsar; Natasha Blanco; Adrián González


Introduction: the non-receptor tyrosine kinase c-Abl (ABL1), is fundamental for multiple cellular processes including proliferation, survival, apoptosis and differentiation. In the context of myogenesis, ABL1 is necessary for myoblast differentiation by mediating activation of the p38α/β MAPK pathway. ABL1 also regulates the activity of the transcription factor MyoD during DNA-damage stress response, pausing differentiation. Moreover, cellular localization of ABL1 is key for proper myogenesis. Now we know that ABL1 loss of function down regulates transcriptional activity an expression of Pax7 and this impair differentiation. However, we do not know which is the impact of this on muscle regeneration and Satellite Cells in the muscle itself. So, the objective of this work is to determine if ABL1 loss of function affects satellite cell’s myogenic capacity in vitro and in vivo and the repercussions on the adult skeletal muscle. Material & Methods: Expression of molecular markers and morphological differentiation, was determined by immunofluorescence and phase contrast microscopy. Satellite cell function during induced muscle injury and regeneration upon ABL1 loss, was evaluated in ABL1fl/fl :Pax7CreERT2 transgenic mice and expression of Pax7, MyoD and myogenin was analyzed by western blot. Results: ABL1 loss, results in down-regulation of Pax7 expression. Interestingly, muscle differentiation was impaired, although MyoD expression was not affected by ABL1 loss of function. Accordingly, satellite cell-specific ABL1 ablation impairs muscle regeneration upon acute injury. Discussion: the results presented here suggest that ABL1 regulates myogenic progression at different levels, affecting, in part, the expression of the early progenitor marker Pax7 and the early differentiation marker myogenin. Ongoing experiments are directed to uncover the molecular pathways involved and these responses ex-vivo and in vivo.

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Fecha de publicación: 2018
Año de Inicio/Término: Octubre
Idioma: Inglés