EGF Mediates Survival of Rat Cochlear Sensory Cells via an NF-κB Dependent Mechanism In Vitro.

Abstract

The survival of cochlear epithelial cells is of considerable importance, biologically. However, little is known about the growth factor(s) that are involved in the survival of cochlear sensory epithelial cells. In this study, we demonstrated that epidermal growth factor (EGF) plays a role in the survival of cochlear epithelial cells. Firstly, the presence of the EGF signaling pathway was demonstrated in the developing cochlear tissues of rats and a sensory epithelial cell line (OC1): -- epidermal growth factor receptor (EGFR), mitogen-activated protein kinase kinase (MAPKK), I kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), and B cell lymphoma 2 (Bcl-2). Secondly, the addition of EGF to OC1 increased the promoter activity of NF-κB and cell viability but not cell cycle progression and cell number increase -- which suggests that EGF is for cellular survival rather than cell proliferation of OC1. Finally, pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) and inhibitor kappa B alpha (IκBα) mutant (IκBαM, a specific inhibitor of NF-κB) abrogated the EGF-induced NF-κB activity and cell survival. These data suggest that EGF plays a role in the survival of cochlear sensory epithelial cells through the EGFR/MAPKK/IκBα/NF-κB/Bcl-2 pathway.