Id1 induces the proliferation of cochlear sensory epithelial cells via the nuclear factor-kappaB/cyclin D1 pathway in vitro.
Inhibitors of differentiation (Id) play an essential role in the neurogenesis of the central nervous system. However, the expression and function of Id in the development of cochlear sensory epithelial cells have yet to be elucidated. In this study, we demonstrate the Id1 gene was expressed in the rapidly growing otocyst on embryonic day 12 (E12) and in the organ of Corti, spiral ganglions, and stria vascularis on postnatal day 1 (P1) by cellular and molecular biologic techniques. Knockdown of the Id1 gene with short interfering RNA (siRNA) in a cochlear sensory epithelial cell line (OC1) significantly reduced its proliferation, whereas overexpression of Id1 in OC1 significantly increased the proliferation of OC1, suggesting a role of Id1 in the development of cochlear sensory epithelial cells. The proliferative action of Id1 on OC1 was mediated by nuclear factor-kappaB (NF-kappaB) and cyclin D1 (a downstream molecule of NF-kappaB). Blockage of the NF-kappaB activity with pyrrolidine dithiocarbamate (PDTC) or enhancement of the NF-kappaB activity with p65 (a subunit of NF-kappaB) in OC1 significantly inhibited or increased, respectively, the cell proliferation and transcription of cyclin D1 induced by Id1. Truncation of the NF-kappaB binding site in the cyclin D1 promoter fully abrogated the transcription of cyclin D1, suggesting that the cyclin D1 transcription is dependent on NF-kappaB. We concluded from this study that Id1 induces the proliferation of OC1 via the NF-kappaB/cyclin D1 pathway.
Ozeki
Masashi
M
Auditory Molecular Biology Laboratory, Department of Otolaryngology University of Minnesota, Minneapolis, Minnesota, USA.
Hamajima
Yuki
Y
Feng
Ling
L
Ondrey
Frank G
FG
Schlentz
Eileen
E
Lin
Jizhen
J
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000502:physiology; D002455:Cell Division; D003051:Cochlea / Q000166:cytology* / Q000196:embryology; D019938:Cyclin D1 / Q000378:metabolism*; D004261:DNA Replication; D018507:Gene Expression Regulation, Developmental; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D009925:Organ of Corti / Q000166:cytology / Q000196:embryology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D016196:S Phase; D013136:Spiral Ganglion / Q000166:cytology / Q000196:embryology
C497454:ID1 protein, rat; D051798:Inhibitor of Differentiation Protein 1; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1