Axin1 up-regulated 1 accelerates stress-induced cardiomyocytes apoptosis through activating Wnt/β-catenin signaling

Stress-induced cardiomyocyte apoptosis contributes to the pathogenesis of a variety of cardiovascular diseases, but how stress induces cardiomyocyte apoptosis remains largely unclear. The present study aims to investigate the effects of Axinl up-regulated 1 (Axudl), a novel pro-apoptotic protein, on the cardiomyocyte survival and the underlying mechanisms. To thig end, a rat model under restraint stress (RS) was established and in vitro stress-induced cardiomyocytes culture was achieved. Our data showed that Axudl was upregulated in the rat myocardia after exposure to RS. Anti-apoptotic Bcl-2 was decreased, whereas pro-apoptotic Box and Cleaved caspase-3 (Cc3) were increased in a time-dependent manner. The Wnt/beta-catenin signaling was observed to be interestingly activated in heart undergoing RS. In addition, the treatment of norepinephrine (NE) to in vitro cardiomyocytes increased Axudl level and induced cell apoptosis. Wnt/j3-catenin signaling was consistently activated. Knockdown of Axudl using specific siRNA blunted NE-induced cardiomyocytes apoptosis and also inactivated the Wnt/beta-catenin signaling. XAV-939, an inhibitor of Wnt/beta-catenin signaling, partially reversed the pro-apoptotic effect of NE. hi conclusion, Axudl accelerated stress-induced cardiomyocytes apoptosis through activation of Wnt/beta-catenin signaling pathway. Our data provided novel evidence that therapeutic strategies against Axudl or Wnt/beta-catenin signaling might be promising in relation to RS-induced myocardial injury.