c-Abl inhibition/loss of function affects myogenic transcription factors expression during adults myoblast differentiation

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

Keywords: satellite cells, c-abl, pax7, Muscle regeneration


Introduction: the non-receptor tyrosine kinase c-Abl, is fundamental for multiple cellular processes including proliferation, survival, apoptosis and differentiation among others. In the context of myogenesis, c-Abl it’s necessary for myoblasts differentiation via interaction with Cdo, a multifunctional membrane receptor, inducing the activation of p38α/β MAPK pathway. Furthermore, this kinase regulates the activity of the transcription factor MyoD during DNA-damage stress response, pausing differentiation. Finally, the cellular localization of c-Abl is key for the correct process of myogenesis. However, it’s not clear if c-Abl modulates other key myogenic transcription factors (e.g. Pax7 or myogenin) during myogenic progression and muscle regeneration. The objective of this work is to determine if c-Abl loss of function alters the expression levels of myogenic transcription factors, affecting, therefore, muscle differentiation and regeneration. Materials & Methods: expression of Pax7, MyoD and myogenin was analyzed by western blot, RT-PCR and immunofluorescence in C2C12 cells treated with c-Abl inhibitor or vehicle. Phase contrast and immunofluorescence microscopy was used for the analysis of marker expression and morphological differentiation. Ablflox/flox/Pax7:CreER transgenic mice were used for in vivo and muscle injury/regeneration experiments. Results: the levels of myogenic transcription factors decreased in both, cells and mice, when c-Abl is lost. On other hand, muscle regeneration is altering. Finally, we observed that differentiation process was altered in C2C12 cells treated with c-Abl inhibitor and in primary myoblast from c-Abl conditional Knockout mice. Discussion: this data suggest that c-Abl participates during the myogenic progression and skeletal muscle regeneration, regulating at least, the myogenic transcription factors levels.

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Fecha de publicación: 2017
Año de Inicio/Término: Octubre
Idioma: Inglés