Cyanidin 3-Glucoside Induces Hepatocyte Growth Factor in Normal Human Dermal Fibroblasts through the Activation of β2-Adrenergic Receptor.

Abstract

Hepatocyte growth factor (HGF) is expressed in various organs and involved in the fundamental cellular functions such as mitogenic, motogenic, and morphogenic activities. Induction of HGF may be therapeutically useful for controlling organ regeneration, wound healing, and embryogenesis. In this study, we examined the stimulation effect of cyanidin 3-glucoside (C3G), an anthocyanidin derivative, on HGF production in normal human dermal fibroblasts (NHDFs) and the underlying mechanisms. C3G induced HGF production at both mRNA and protein levels in NHDF cells and enhanced the phosphorylation of cAMP-response element-binding protein. We also observed that treatment with C3G increased intracellular cAMP level and promoter activity of cAMP-response element in HEK293 cells expressing β2-adrenergic receptor (β2AR). In contrast, cyanidin, an aglycon of C3G, did not show the activation of β2AR signaling and HGF production. These results indicate that C3G behaves as an agonist for β2AR signaling to activate the protein kinase A pathway and induce the production of HGF.