Cotransfection of Pax2 and Math1 promote in situ cochlear hair cell regeneration after neomycin insult.

Cotransfection of Pax2 and Math1 promote in situ cochlear hair cell regeneration after neomycin insult.
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Pax2 和 Math1 共转染促进新霉素损伤后原位耳蜗毛细胞再生

DOI:
10.1038/srep02996
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发表时间:
2013-10-21
期刊:
影响因子:
4.6
通讯作者:
Li, Huawei
Li, Huawei
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen, Yan;Yu, Huiqian;Zhang, Yanping;Li, Wen;Lu, Na;Ni, Wenli;He, Yingzi;Li, Jin;Sun, Shan;Wang, Zhengmin;Li, Huawei

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毛细胞再生的理想策略是促进残余支持细胞增殖,然后诱导毛细胞分化。在这项研究中,用新霉素处理培养的新生小鼠Corti器官以消除毛细胞,然后与表达Pax 2和/或Math 1的重组腺病毒一起孵育。结果表明,Pax 2过表达可显著促进支持细胞的增殖。腺病毒感染后2周,Ad-Pax 2-IRES-Math 1组毛细胞预存区BrdU +/myosin VIIA+细胞数较Ad-Pax 2和Ad-Math 1组明显增加。这表明Pax 2和Math 1共转染可诱导支持细胞增殖并原位分化为毛细胞。大多数新生毛细胞被FM 1 -43标记,表明它们获得了一定的功能。结果还表明,通过强制表达Math 1诱导增殖细胞而不是静止细胞分化为毛细胞对于哺乳动物毛细胞再生是可行的。
The ideal strategy for hair cell regeneration is promoting residual supporting cell proliferation followed by induction of hair cell differentiation. In this study, cultured neonatal mouse organs of Corti were treated with neomycin to eliminate hair cells followed by incubation with recombined adenovirus expressing Pax2 and/or Math1. Results showed that overexpression of Pax2 significantly promoted proliferation of supporting cells. The number of BrdU⁺/myosin VIIA⁺ cells increased significantly in hair cell pre-existing region two weeks after adenovirus infection in Ad-Pax2-IRES-Math1 group compared to Ad-Pax2 and Ad-Math1 groups. This indicated that cotransfection of Pax2 and Math1 induced supporting cells to proliferate and differentiate into hair cells in situ. Most new hair cells were labeled by FM1-43 suggesting they acquired certain function. The results also suggest that inducing proliferating cells rather than quiescent cells to differentiate into hair cells by forced expression of Math1 is feasible for mammalian hair cell regeneration.
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