Silencing p27 reverses post-mitotic state of supporting cells in neonatal mouse cochleae
Silencing p27 reverses post-mitotic state of supporting cells in neonatal mouse cochleae
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DOI：
10.1016/j.mcn.2009.08.011
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发表时间：
2009-11-01
影响因子：
3.5
通讯作者：
Ito, Juichi
中科院分区：
文献类型：
--
作者：
Ono, Kazuya;Nakagawa, Takayuki;Ito, Juichi
出生后的耳蜗哺乳动物上皮细胞没有能力在组织中增殖，然而，解离的支持细胞表现出分裂和转分化成新的毛细胞在体外的能力，这一过程被发现与细胞周期蛋白依赖性激酶抑制剂p27（kip1）的下调。在这里，我们表明，敲低p27（kip1）与短发夹RNA表达载体的结果在有丝分裂后的支持细胞在出生后的小鼠耳蜗离体细胞周期重新进入。p27（kip1）基因敲除的细胞掺入BrdU后分裂为两个子细胞。然而，在一些支持细胞中也存在凋亡途径的激活。这些结果表明，使用RNA干扰靶向p27（kip1）是一种有效的策略，诱导细胞周期再入有丝分裂后的支持细胞在出生后的哺乳动物耳蜗，虽然额外的操作的支持细胞需要实现毛细胞再生。(C)2009 Elsevier Inc. All rights reserved.
The post-natal cochlear mammalian epithelium have no capacity to proliferate in tissue, however, dissociated supporting cells exhibit the ability to divide and trans-differentiate into new hair cells in vitro, with this process found to be correlated with the downregulation of the cyclin-dependent kinase inhibitor p27(kip1). Here we show that knockdown of p27(kip1) with short hairpin RNA-expressing vectors results in the cell-cycle reentry of post-mitotic supporting cells in the post-natal mouse cochleae ex vivo. The p27(kip1)-knockdown cells incorporated BrdU, and then divided into two daughter cells. However, there was also activation of the apoptotic pathway in some supporting cells. These results indicate that the use of RNA interference to target p27(kip1) is an effective strategy for inducing cell-cycle reentry in post-mitotic supporting cells in the post-natal mammalian cochleae, although additional manipulations of the supporting cells are required to achieve hair cell regeneration. (C) 2009 Elsevier Inc. All rights reserved.