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CTNNB1 inhibits SCN5A. 9 / 9
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"Conclusions Enhancement of beta-catenin / TCF4 signaling suppressed NaV1.5 expression and inhibited Na + channel activity , leading to prolongation of the QRS complex and increased susceptibility to VT in mice ."
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"3.7 TCF4 was required for beta-catenin inhibition of SCN5a promoter activity."
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"24 We found that ROS inhibited cardiac Na + channel activity by suppressing NaV1.5 expression24 through enhancing beta-catenin / TCF4 signaling ,17 and that NaV1.5 expression in peri-infarct zone ( PIZ ) of mouse hearts with myocardial infarction ( MI ) was significantly decreased.6 Future studies will be focused on determining if TCF4 is required to for suppression of NaV1.5 by beta-catenin and if its deletion is able to prevent the downregulation of NaV1.5 in PIZ of mouse hearts with MI and cardiac electrical remodeling , as well as the decrease in Na + activity in cardiomyocytes in the PIZ ."
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"Beta-catenin inhibition of SCN5a promoter activity was in a concentration dependent manner (XREF_FIG)."
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"Similarly, inhibition of Wnt signaling using shRNA-mediated β-catenin knockdown in BrS iPSC-CMs led to a 4.0-fold increase in Na v 1.5, which was associated with a 4.9-fold increase in peak I Na but only a 2.1-fold increase in SCN5A mRNA."
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"However, the SCN5a promoter activity was significantly increased (p < 0.01) by TCF4 siRNA in the presence of beta-catenin, indicating that beta-catenin inhibition of SCN5a promoter activity is dependent on the presence of TCF4 (XREF_FIG)."
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"Luciferase promoter assays exhibited that beta-catenin inhibited the SCN5a promoter activity at a dose dependent manner and this inhibition required TCF4."
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"The results revealed that both beta-catenin overexpression and LiCl significantly inhibited the SCN5a promoter activity as compared to the control (p < 0.01) (XREF_FIG)."
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"TCF4 SiRNA was used to confirm that beta-catenin inhibition of SCN5a promoter activity requires TCF4."
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