Bone morphogenetic protein 4, inhibitor of differentiation 1, and epidermal growth factor receptor regulate the survival of cochlear sensory epithelial cells

Abstract

Bone morphogenetic protein 4 (BMP4) is crucial for the development of the inner ear, but the mechanism of how BMP4 affects this process remains unknown. The focus of this research was to determine whether BMP4 can regulate the survival of cochlear sensory epithelial cells through inhibitor of differentiation 1 (Id1) and the epidermal growth factor receptor (EGFR). In this study, we first investigated the effects of BMP4, noggin, and dominant negative BMPR1B (dnBMPR1B) on the proliferation and survival of cochlear sensory epithelial cells. Subsequently, we investigated the influences of BMP4, noggin, and dnBMPR1B on the expression of Id1 and EGFR. We found that BMP4 had a negative effect on cell survival and on Id1 and EGFR expression in vitro, whereas noggin and dnBMPR1B treatment had positive effects. Knockdown of the Id1 gene with short interfering RNA (siRNA) reduced the expression of EGFR and cell proliferation. These data suggest that BMP4 may regulate survival through the Id1/EGFR pathway during development of the rat inner ear.