The stat3/socs3a pathway is a key regulator of hair cell regeneration in zebrafish. [corrected].
The stat3/socs3a pathway is a key regulator of hair cell regeneration in zebrafish. [corrected].
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DOI：
10.1523/jneurosci.5785-10.2012
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发表时间：
2012-08-01
期刊：
影响因子：
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通讯作者：
Burgess SM
中科院分区：
文献类型：
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作者：
Liang J;Wang D;Renaud G;Wolfsberg TG;Wilson AF;Burgess SM
所有研究的非哺乳类脊椎动物都可以再生内耳机械感受器，即毛细胞，但哺乳动物出生后再生的能力非常有限。因此，一旦失去内耳毛细胞，哺乳动物就会遭受永久性的听力和平衡缺陷。毛细胞再生的机制知之甚少。由于内耳感觉上皮在所有脊椎动物中高度保守，因此我们选择成年斑马鱼作为研究对象，研究其毛细胞再生的机制，希望其研究结果能够应用于哺乳动物毛细胞的诱导再生。我们利用强大的转录分析技术数字基因表达（DGE）定义了成年斑马鱼内耳毛细胞再生相关基因的综合网络，该技术利用了下一代测序的力量。我们还确定了一个关键的途径，stat 3/socs 3，并证明了其在促进毛细胞再生通过干细胞活化，细胞分裂和分化的作用。此外，stat 3信号的瞬时药理学上调加速了毛细胞再生，而没有过度产生细胞。考虑到其他已发表的数据集，我们提出stat 3/socs 3通路是所有组织再生中的关键反应，因此是组织修复和损伤愈合中广泛应用的重要治疗靶点。
All nonmammalian vertebrates studied can regenerate inner ear mechanosensory receptors, i.e. hair cells, but mammals only possess a very limited capacity for regeneration after birth. As a result, mammals suffer from permanent deficiencies in hearing and balance once their inner ear hair cells are lost. The mechanisms of hair cell regeneration are poorly understood. Because the inner ear sensory epithelium is highly conserved in all vertebrates, we chose to study hair cell regeneration mechanism in adult zebrafish, hoping the results would be transferrable to inducing hair cell regeneration in mammals. We defined the comprehensive network of genes involved in hair cell regeneration in the inner ear of adult zebrafish with the powerful transcriptional profiling technique, Digital Gene Expression (DGE), which leverages the power of next-generation sequencing. We also identified a key pathway, stat3/socs3, and demonstrated its role in promoting hair cell regeneration through stem cell activation, cell division, and differentiation. In addition, transient pharmacological up-regulation of stat3 signaling accelerated hair cell regeneration without over-producing cells. Taking other published datasets into account, we propose that the stat3/socs3 pathway is a key response in all tissue regeneration and thus an important therapeutic target for a broad application in tissue repair and injury healing.