Sphingosine 1-phosphate (S1P) signaling is required for maintenance of hair cells mainly via activation of S1P2
Sphingosine 1-phosphate (S1P) signaling is required for maintenance of hair cells mainly via activation of S1P2
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DOI：
10.1523/jneurosci.4245-06.2007
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发表时间：
2007-02-07
影响因子：
5.3
通讯作者：
Chun, Jerold
中科院分区：
文献类型：
--
作者：
Herr, Deron R.;Grillet, Nicolas;Chun, Jerold
听觉需要耳蜗中被称为毛细胞的特化上皮细胞对振动力进行转换。人耳含有有限数量的终末分化的毛细胞，一旦因噪声引起的损伤或毒性损伤而丢失，就永远无法再生。我们在这里报告，鞘氨醇1-磷酸（S1 P）信号，主要通过激活其同源受体S1 P（2），是维持前庭和耳蜗毛细胞在体内所必需的。反转录-PCR和原位杂交结果表明，耳蜗中存在两种S1 P受体，S1 P（2）和S1 P（3）。这两种受体均无效的小鼠一致地显示出进行性耳蜗和前庭缺陷，伴有毛细胞损失，导致4周龄时完全耳聋，并且随着完全耳聋，平衡缺陷的严重程度增加。这项研究揭示了S1 P信号在维持耳蜗和前庭完整性中的作用，并提出了退行性听力损失治疗干预的方法。
Hearing requires the transduction of vibrational forces by specialized epithelial cells in the cochlea known as hair cells. The human ear contains a finite number of terminally differentiated hair cells that, once lost by noise-induced damage or toxic insult, can never be regenerated. We report here that sphingosine 1-phosphate (S1P) signaling, mainly via activation of its cognate receptor S1P(2), is required for the maintenance of vestibular and cochlear hair cells in vivo. Two S1P receptors, S1P(2) and S1P(3), were found to be expressed in the cochlea by reverse transcription-PCR and in situ hybridization. Mice that are null for both these receptors uniformly display progressive cochlear and vestibular defects with hair cell loss, resulting in complete deafness by 4 weeks of age and, with complete penetrance, balance defects of increasing severity. This study reveals the previously unknown role of S1P signaling in the maintenance of cochlear and vestibular integrity and suggests a means for therapeutic intervention in degenerative hearing loss.