Xue Tao, Wei Li, Zha Ding-Jun, Qiao Li, Lu Lian-Jun, Chen Fu-Quan, Qiu Jian-Hua
Department of Otolaryngology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Int J Mol Med. 2015 Mar;35(3):637-44. doi: 10.3892/ijmm.2015.2075. Epub 2015 Jan 21.
Stem cell therapy has attracted widespread attention for a number of diseases. Recently, neural stem cells (NSCs) from the cochlear nuclei have been identified, indicating a potential direction for the treatment of sensorineural hearing loss. Acoustic stimuli play an important role in the development of the auditory system. In this study, we aimed to determine whether acoustic stimuli induce NSC development and differentiation through the upregulation of clusterin (CLU) in NSCs isolated from the cochlear nuclei. To further clarify the underlying mechanisms involved in the development and differentiation of NSCs exposed to acoustic stimuli, we successfully constructed animal models in which was CLU silenced by an intraperitoneal injection of shRNA targeting CLI. As expected, the NSCs from rats treated with LV-CLU shRNA exhibited a lower proliferation ratio when exposed to an augmented acoustic environment (AAE). Furthermore, the inhibition of cell apoptosis induced by exposure to AAE was abrogated after silencing the expression of the CLU gene. During the differentiation of acoustic stimuli-exposed stem cells into neurons, the number of astrocytes was significantly reduced, as evidenced by the expression of the cell markers, microtubule associated protein‑2 (MAP-2) and glial fibrillary acidic protein (GFAP), which was markedly inhibited when the CLU gene was silenced. Our results indicate that acoustic stimuli may induce the development and differentiation of NSCs from the cochlear nucleus mainly through the CLU pathway. Our study suggests that CLU may be a novel target for the treatment of sensorineural hearing loss.
干细胞疗法已在多种疾病中引起广泛关注。最近,已鉴定出耳蜗核中的神经干细胞(NSCs),这为感音神经性听力损失的治疗指明了一个潜在方向。声刺激在听觉系统发育中起重要作用。在本研究中,我们旨在确定声刺激是否通过上调从耳蜗核分离的神经干细胞中的簇集蛋白(CLU)来诱导神经干细胞的发育和分化。为了进一步阐明参与暴露于声刺激的神经干细胞发育和分化的潜在机制,我们成功构建了通过腹腔注射靶向CLU的短发夹RNA(shRNA)使CLU沉默的动物模型。正如预期的那样,用LV-CLU shRNA处理的大鼠的神经干细胞在暴露于增强声环境(AAE)时增殖率较低。此外,在沉默CLU基因的表达后,由暴露于AAE诱导的细胞凋亡抑制作用被消除。在暴露于声刺激的干细胞向神经元分化的过程中,星形胶质细胞的数量显著减少,这通过细胞标志物微管相关蛋白-2(MAP-2)和胶质纤维酸性蛋白(GFAP)的表达得到证明,当CLU基因沉默时,这种表达受到明显抑制。我们的结果表明,声刺激可能主要通过CLU途径诱导耳蜗核神经干细胞的发育和分化。我们的研究表明,CLU可能是治疗感音神经性听力损失的一个新靶点。