Supporting cells eliminate dying sensory hair cells to maintain epithelial integrity in the avian inner ear.
Supporting cells eliminate dying sensory hair cells to maintain epithelial integrity in the avian inner ear.
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DOI：
10.1523/jneurosci.3042-10.2010
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发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Gale JE
中科院分区：
文献类型：
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作者：
Bird JE;Daudet N;Warchol ME;Gale JE
上皮内稳态对于内耳听觉和前庭器官的感觉转导是必不可少的，但它是如何在创伤中维持的还知之甚少。为了研究潜在的修复机制，我们在鸡的内耳中表达了β-肌动蛋白-绿色荧光蛋白，并使用活细胞成像技术研究了感觉上皮在氨基糖苷类药物诱导的毛细胞损伤中的反应。我们发现，胶质样支持细胞使用两种独立的机制来快速消除濒临死亡的毛细胞。支持细胞在管腔表面组装一条肌动蛋白缆索，该缆索围绕角质层连接并收缩，从毛细胞胞体中切除静毛纤毛束和角质板。毛束切除可以在肌动蛋白电缆形成后3分钟内进行。在束切除后，通常在延迟2-3小时后，支持细胞吞噬并吞噬剩余的无束毛细胞。β-肌动蛋白-绿色荧光蛋白和活性染料的双通道记录显示，吞噬作用与毛细胞完整性的丧失是同时发生的。我们得出的结论是，支持细胞在毛细胞质膜完整性丧失之前修复了上皮屏障，支持细胞的活性与毛细胞死亡密切相关。用Rho-Kinase抑制剂Y-27632治疗并没有阻止束状切除，但延长了吞噬细胞的时间，并导致毛细胞身体聚集在上皮内。我们的数据显示，支持细胞不仅在创伤期间维持上皮完整性，而且表明它们也可能是毛细胞死亡过程本身不可或缺的一部分。
Epithelial homeostasis is essential for sensory transduction in the auditory and vestibular organs of the inner ear, but how it is maintained during trauma is poorly understood. To examine potential repair mechanisms, we expressed β-actin-EGFP in the chick inner ear and used live-cell imaging to study how sensory epithelia responded during aminoglycoside-induced hair cell trauma. We found that glial-like supporting cells used two independent mechanisms to rapidly eliminate dying hair cells. Supporting cells assembled an actin cable at the luminal surface that extended around the peri-cuticular junction and constricted to excise the stereocilia bundle and cuticular plate from the hair cell soma. Hair bundle excision could occur within 3 minutes of actin-cable formation. Following bundle excision, typically after a delay of up to 2–3 hours, supporting cells engulfed and phagocytosed the remaining bundle-less hair cell. Dual-channel recordings with β-actin-EGFP and vital dyes revealed phagocytosis was concurrent with loss of hair cell integrity. We conclude that supporting cells repaired the epithelial barrier before hair cell plasmalemmal integrity was lost and that supporting cell activity was closely linked to hair cell death. Treatment with the Rho-kinase inhibitor Y-27632 did not prevent bundle excision but prolonged phagocytic engulfment and resulted in hair cell corpses accumulating within the epithelium. Our data show that supporting cells not only maintain epithelial integrity during trauma but suggest they may also be an integral part of the hair cell death process itself.