ABL1 loss of function affects myogenic transcription factors expression during adults myoblast differentiation.

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


Background: 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 via interaction with the receptor Cdo, 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. However, it’s not clear if ABL1 modulates other key transcription factors in the muscle lineage, such as Pax7 and myogenin, during muscle formation. The objective of this work is to determine if ABL1 loss of function affects satellite cell’s myogenic capacity in vitro and in vivo. Methods: expression of Pax7, MyoD and myogenin was analyzed by western blot, RT-PCR and immunofluorescence in C2C12 cells treated with ABL1 inhibitor (imatinib), activator (DPH) or vehicle. 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. Results: ABL1 inhibition/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. Conclusion: 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: Junio
Idioma: Inglés