Tbx20 promotes H9c2 cell survival against oxidative stress and hypoxia in vitro

ABSTRACT

Sustained and cardiac injury specific overexpression of Tbx20 provide cardiac protection of adult heart by preserving cardiac function increasing its survival rate post myocardial infarction (MI). However, the molecular mechanism underlying this protective pathway is largely unknown. Thus, in the current study, we examined Tbx20 and associated protective signaling pathway against two specific injury inductions. Injury inductions were done by imparting the cultured cardiac H9c2 cells with oxidative stress and hypoxia. Both stresses resulted in increased Tbx20 expression which activated the level of Nmyc1 and Bmp2 showing increased cellular proliferative rate. However, it was not sufficient to overcome the stress responses owing to increased apoptosis. The sustained overexpression of Tbx20, prior to injury induction, showed further enhancement in the expression patterns of Nmyc1 and Bmp2 that accelerated the proliferation rate, thus promoting the formation of increased number of viable cells, reducing the cellular apoptosis post injury. Moreover, overexpressed Tbx20 inhibits cellular hypertrophy post injury by increasing the activation level of Yap1 and together may follow a feedback loop mechanism downregulating the p-Akt activity. Therefore, Tbx20 overexpression has been found to be sufficient to impart cardiac protection post injury by triggering its associated signaling molecules.