Granulocyte colony-stimulating factor activates Wnt signal to sustain gap junction function through recruitment of beta-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, beta-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.
Kuwabara
Masanori
M
Department of Medicine and Geriatrics, Kochi Medical School, Nankoku, Japan.
Kakinuma
Yoshihiko
Y
Katare
Rajesh G
RG
Ando
Motonori
M
Yamasaki
Fumiyasu
F
Doi
Yoshinori
Y
Sato
Takayuki
T
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015820:Cadherins / Q000032:analysis; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000032:analysis / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000032:analysis
D000889:Anti-Arrhythmia Agents; D015820:Cadherins; D018031:Connexin 43; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D051153:Wnt Proteins; D051176:beta Catenin; D016179:Granulocyte Colony-Stimulating Factor