| In recent years, hair cell regeneration/self-repair has been the intensive spot of inner ear research area. The latest study has demonstrated that lesioned vestibular epithelium has the capacity to self-repair to a certain degree. Several signaling transduction mechanisms are involved in this process .ObjectiveTo study the changes of cell proliferation during hair cell self-repair after vestibular epithelium was lesioned and to elucidate the molecular mechanisms of the related signal transduction pathway, which may lay a foundation for further study on hah" cell regeneration /self-repair.MethodsK 5-bromo-2-deoxyuridine was in vivo labeled and anti-Brdu immuno-histochemistry was used to detecte the changes of the cell proliferation of vestibular epithelium during hair cell self-repair. The expression and distribution of insulin-like growth factor-1 (IGF-1 ) and its receptor (IGF-1R) were detected by anti-IGF-1 and anti-IGF-lR, which is to elucidate the relationship between IGF-1 and cell proliferation and its function during hair cell self-repair.2^ The expression and distribution of extracellular signal regulated kinase 1/2 (ERK1/2) in vestibular epithelium was detected by anti-ERK-1 and anti-ERK2 immunocytochemistry.3 -. The expression of STADmRNA was examined by in situ hybridizationusing digoxin-labelled oligonucleotide probe. Results1. The relationship between cell proliferation and the expression of IGF-1 and its receptor during hair cell self-repair in vestibular epithelium of guinea pig after gentamicin toxicityBrdu immunopositive cells were not detected in the control group, but observed in all the experimental groups. Id after gentamicin treatment, Brdu positive cells were mainly seen in supporting cells and the number of positive cells was the largest in 7d group, in both supporting cells and hair cells. Then the number of Brdu positive cells decreased gradually (/*< 0. 05).In21d group, the positive cells could still be seen, and were mainly located hi hair cells.In the control group, the expression of IGF-1 and IGF-1R was low in vestibular epithelium. Whereas, it was elevated significantly in Id group and increased to its maximum, mainly located in the cytoplasm of hair cells. Then the expression of IGF-1 and its receptor decreased gradually (P < 0.05) . The expression changes of IGF-1 and its receptor were similar.2. The expression of ERK1/2 in vestibular epithelium of guinea pig after gentamicin toxicityhnmunoreactivity of ERK1/2 was low in the control group , while elevated significantly after gentamycin toxicity, and increased to its maximum after 1 week. Then the levels of ERK1/2 decreased gradually (P< 0. 01), but were still higher than the control group at 2Id. There was no obvious differences in expressions of ERK1/2 among different groups.3. The expression changes of STAT3mRNA in vestibular epithelium of guinea pig after gentamicin toxicityIn the vestibular epithelium of adult guinea pigs, the expression levels of STATSmRNA were low hi the control group, while elevated significantly after gentamycin treatment, and increased to the peak at 1 day group. After that itdecreased gradually, and there was no significant difference between the 2Id and the control group.Conclusion1. After gentamycin treatment, the epithelia cells in vestibular end organs of guinea pigs begun to proliferate, and the cell proliferation diminished with recovery processing. The expression of IGF-1 and its receptor in vestibular epithelium increased after gentamycin treatment, and IGF-1, which correlated well with cell proliferation, may be the endogenous mitogen through a paracrine or autocrine manner during hair cell self-repair of guinea pig. IGF-1 may play an important role in early stage of hair cell self-repair.2. The expression levels of ERK1/2 in vestibular epithelium of guinea pigs increased after gentamicin toxicity. Furthermore, the time course of the expression of ERK1/2 coincided with the proliferation of vestibular epithelial cells. Therefore, ERK1/2...
|
PDF Full Text Request