Granulocyte colony-stimulating factor activates Wnt signal to sustain gap junction function through recruitment of β-catenin and cadherin

Our previous study reveals that connexin (Cx) 43 is targeted by ACh to prevent lethal arrhythmia. Granulocyte colony-stimulating factor (G-CSF), used against ischemic heart failure, may be another candidate, however, with unknown mechanisms. Therefore, we investigated the cellular effects of G-CSF. G-CSF activated the Wnt and Jak2 signals in cardiomyocytes, and up-regulated Cx43 protein and phosphorylation levels. In addition, G-CSF enhanced the localization of Cx43, β-catenin and cadherin on the plasma membrane. G-CSF inhibited the reduction of Cx43 by enhancing Cx43 anchoring and sustained the cell–cell communication during hypoxia. Consequently, G-CSF suppressed ventricular arrhythmia induced by myocardial infarction. As a result, G-CSF could be used as a therapeutic tool for arrhythmia.