Hepatocyte Growth Factor Protects Auditory Hair Cells From Aminoglycosides
Hepatocyte Growth Factor Protects Auditory Hair Cells From Aminoglycosides
复制标题
DOI：
10.1002/lary.20602
复制
发表时间：
2009-10-01
期刊：
影响因子：
2.6
通讯作者：
Ito, Juichi
中科院分区：
文献类型：
--
作者：
Kikkawa, Yayoi S.;Nakagawa, Takayuki;Ito, Juichi
目的/假设：探讨肝细胞生长因子（HGF）对听毛细胞抗氨基糖苷的保护作用及其分子机制。研究设计：实验研究。方法：采用外植体培养系统定量评价HGF对小鼠耳蜗毛细胞抗新霉素毒性的保护作用。为了了解HGF对毛细胞的保护机制，我们采用免疫组织化学和Western blotting方法检测了耳蜗中c-Met、HGF受体和4-羟基壬烯醛（一种脂质过氧化标志物）的表达。结果：HGF用于耳蜗外植体培养可显著减少新霉素诱导的耳蜗毛细胞丢失。免疫组化显示c-Met在正常听毛细胞中表达，并对新霉素诱导的损伤反应增加。4-羟基壬烯醛免疫染色提示HGF通过减轻新霉素诱导的听上皮脂质过氧化作用。结论：这些发现表明耳蜗中存在功能性HGF/c-Met偶联，HGF对毛细胞具有保护作用，提示HGF有可能作为感音神经性听力损失的治疗剂。
Objectives/Hypothesis: To examine the effect of hepatocyte growth factor (HGF) for protection of auditory hair cells against aminoglycosides and its molecular mechanisms.Study Design: Experimental study.Methods: We quantitatively assessed protective effects of HGF on mouse cochlear hair cells against neomycin toxicity using explant culture systems. To understand mechanisms of hair cell protection by HGF, we examined the expression of c-Met, HGF receptor, and 4-hydroxynonenal (a lipid peroxidation marker) in the cochlea by means of immunohistochemistry and Western blotting.Results: The application of HGF to cochlear explant cultures significantly reduced the hair cell loss induced by neomycin. Immunohistochemistry showed c-Met expression in normal auditory hair cells, and its increase in response to neomycin-induced damage. Immunostaining for 4-hydroxynonenal suggested that HGF acted by attenuating the lipid peroxidation of auditory epithelia induced by neomycin.Conclusions: These findings demonstrate that a functional HGF/c-Met coupling is present in the cochlea, and HGF application exerts protective effects on hair cells, indicating the potential of HGF as a therapeutic agent for sensorineural hearing loss.