Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Shandong Provincial Key Laboratory of Otology, Jinan, China.
Sci Rep. 2017 Jan 23;7:41094. doi: 10.1038/srep41094.
c-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb. We then knocked down c-Myb expression with shRNA transfection in HEI-OC1 cells and found that c-Myb knockdown decreased cell viability, increased expression of pro-apoptotic factors, and enhanced cell apoptosis after neomycin insult. Mechanistic studies revealed that c-Myb knockdown increased cellular levels of reactive oxygen species and decreased Bcl-2 expression, both of which are likely to be responsible for the increased sensitivity of c-Myb knockdown cells to neomycin. This study provides evidence that c-Myb might serve as a new target for the prevention of aminoglycoside-induced HC loss.
c-Myb 是一种转录因子，在细胞增殖、分化和凋亡中发挥关键作用。据报道，c-Myb 在鸡耳胚中表达，但 c-Myb 是否存在于哺乳动物耳蜗中，以及它如何发挥作用，尚未得到探索。在这里，我们研究了 c-Myb 在出生后小鼠耳蜗和 HEI-OC1 细胞中的表达，发现 c-Myb 在小鼠耳蜗的毛细胞 (HCs) 以及培养的 HEI-OC1 细胞中表达。接下来，我们证明 c-Myb 的表达在耳蜗 HCs 和 HEI-OC1 细胞中均因新霉素处理而降低，表明 c-Myb 具有耳保护作用。然后，我们通过 shRNA 转染在 HEI-OC1 细胞中敲低 c-Myb 的表达，发现 c-Myb 敲低降低了细胞活力，增加了促凋亡因子的表达，并增强了新霉素损伤后的细胞凋亡。机制研究表明，c-Myb 敲低增加了细胞内活性氧的水平，并降低了 Bcl-2 的表达，这两者都可能导致 c-Myb 敲低细胞对新霉素的敏感性增加。这项研究提供了证据表明，c-Myb 可能成为预防氨基糖苷类抗生素诱导的 HC 损失的新靶点。
