α-E-Catenin is a potential regulator of canonical Wnt and HIPPO-signallings in myocardium

Abstract

The structural integrity of the myocardium is necessary for heart function and maintains by intercalated disks. Alpha-E-catenin – is important component of adherens junction in adult myocardium. In addition, during last time the possible signalling function of a-E-catenin was described. The aim of our work was to investigate the α-E-catenin regulatory function in canonical Wnt and HIPPO signalling in adult heart. Materials and methods. Our work was done with α- E-catenin conditional knockout mice and aMHC-Cre - transgenic animals using. Expression of genes involved in the canonical Wnt- and HIPPO signalling were analysed with rtPCR using. Canonical Wnt signalling activity was investigated by Western blot analysis. Result. We have shown that both heterozygous and homozygous deletion of α-E-catenin gene in the embryonic heart leads to activation of WNT / β-catenin signalling, namely we registered the higher level of c-Fos, c-Myc and Ctnnb1 genes expression and increasing of phosphorylated GSK3β in adult heart. In addition, we observed the HIPPO-signalling pathway activation after α- E-catenin gene ablation, namely we observed increasing of Ctgf, Il1rl1, Tnfrsf1b, Aurka genes expression. Conclusions. Α-E-catenin has an important signalling function in adult heart, namely α-E-catenin regulates cytoplasmic level of main transcriptional activators of the canonical Wnt- and HIPPO - signalling cascades: β-catenin and Yap what leas to limiting their signalling activity. Keywords: α-E-catenin, β-catenin, HIPPO, Wnt-signalling, gene expression, myocardium