The Signal Transduction Of Cell Proliferation And Apoptosis In Vestibular Epithelium During The Development Of Guinea Pig

Hair cell regeneration/repair is the hotspot of inner ear studying area. The lasted study indicated that damage may induce inner ear epithelium to go back and acquire immature properties typical of earlier developmental stages, such as several signaling transduction mechanisms. In this study, cell proliferation was detected by proliferation cell nuclear antigen (PCNA) immunocytochemistry while apoptosis by TdT-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method and transmission electro-microscopy. The cell proliferation and apoptosis of vestibular epithelium in normal developing guinea pig were observed to elucidate the relationship and effect between proliferation and apoptosis in developing vestibular epithelium. The expression of IGF-1 and its receptor was detected by anti-IGF-1 and anti-IGF-lR, which is to elucidate the function of IGF-1 and the relationship with cell proliferation. The expression of ERK1/2 was detected by anti-ERK-1 and anti-ERK2 immunocytochemistry, while the activation of ERKs was detected by Weston blot. This study might lay a foundation for further study on the molecular mechanism of hair cell regeneration /repair. RESULTS1. The relationship between cell proliferation and apoptosis of vestibular epithelium during the development of guinea pig PCNA staining had been detected in supporting cells while hair cells were negative, and the positive cells were decrease with aging (KO. 05) . Thedifferentiated hair cells and supporting cells undergo apoptosis in vestibular sensory epithelium, and TUNEL-positive cells were also markedly decrease with aging (P><0. 01). After birth, TUNEL-positive hair cells located at the top of ampulla. Apoptosis of hair cell and supporting cell can be detected by electron micrograph. The chromatin of nuclear has aggregated into cell-defined clumps.2. The expression and function of IGF-1 and IGF-1R in vestibular epithelium during the development of guinea pigImmuno-reactivity to IGF-1 and its receptor was detected in hair cell and supporting cell of the vestibular sensory epithelium of guinea pig, and the quantity of staining was decrease with aging (P<0. 01).3. The expression and function of ERK1/2 in vestibular epithelium during the development of guinea pigImmuno-reactivity of ERK1 and ERK2 were detected in the vestibular sensory epithelium of guinea pig, and the quantity of staining was decrease with aging (P<0. 01) . The activation of ERKs was also decline with aging, and the activation of ERK2 was higher than that of ERK1. CONCLUSION1. During the development of guinea pig, cell proliferation as well as apoptosis events diminish contemporarily. The balance between proliferation and apoptosis may be regulate the normal number of cells, and relate to guarantee the normal structure and function of inner ear.2. IGF-1 and its receptor were expressed in vestibular sensory epithelium, and IGF-1, which concomitant with cell proliferation, maybe the endogenous insulin-like activity as a paracrine or autocrine manner during the normal ear development of guinea pig. IGF-1 plays multiple roles during ear development, including regulation of proliferation and differentiation in early stage, and control neuronal generation and cellsurvival later.3.ERK1/2 were expressed in vestibular sensory epithelium, which concomitant with cell proliferation and differentiation during the normal ear development of guinea pig. ERK1/2 play an important role in signal transduction pathway of proliferation and differentiation during ear development.