microRNA‑183 is involved in the differentiation and regeneration of Notch signaling‑prohibited hair cells from mouse cochlea.
microRNA‑183 is involved in the differentiation and regeneration of Notch signaling‑prohibited hair cells from mouse cochlea.
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microRNA183 参与小鼠耳蜗 Notch 信号传导抑制毛细胞的分化和再生。
DOI：
10.3892/mmr.2018.9127
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发表时间：
2018-08
影响因子：
3.4
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Zhou W;Du J;Jiang D;Wang X;Chen K;Tang H;Zhang X;Cao H;Zong L;Dong C;Jiang H
损伤后的听觉毛细胞再生是听力恢复的关键。Notch信号通路参与了内耳发育和细胞分化的调节。最近的证据表明，microRNA(MiR)-183在内耳中也有类似的作用。然而，目前尚不清楚Notch信号在哺乳动物毛细胞再生中的作用，也不清楚Notch信号与miR-183之间是否存在串扰。本研究采用庆大霉素诱导的小鼠耳蜗性损伤模型。庆大霉素对毛细胞的损伤激活了Notch信号通路，下调了miR-183的表达。γ分泌酶抑制剂24-二氨基-5-苯基噻唑对Notch信号的抑制可减轻庆大霉素诱导的毛细胞丢失，并逆转miR-183表达的下调。进一步的研究发现，在DAPT诱导下产生的新型毛细胞来自转分化的支持细胞。此外，在体外培养的新生小鼠内耳前体细胞实验中，抑制Notch信号可增加肌球蛋白VI阳性毛细胞的数量。这一作用可被miR-183抑制逆转。这些发现表明，Notch信号通路在毛细胞再生过程中起着抑制作用。抑制这一信号可以改善庆大霉素损伤的耳蜗毛细胞再生。MIR-183被证明参与毛细胞的分化和再生，并且是Notch抑制的毛细胞分化所必需的。
Auditory hair cell regeneration following injury is critical to hearing restoration. The Notch signaling pathway participates in the regulation of inner ear development and cell differentiation. Recent evidence suggests that microRNA (miR)-183 has a similar role in the inner ear. However, it is unclear how Notch signaling functions in hair cell regeneration in mammals and if there is cross-talk between Notch signaling and miR-183. The present study used a gentamicin-induced cochlear injury mouse model. Gentamicin-induced damage of the hair cells activated the Notch signaling pathway and downregulated miR-183 expression. Notch signaling inhibition by the γ-secretase inhibitor, 24-diamino-5-phenylthiazole (DAPT), attenuated gentamicin-induced hair cell loss and reversed the downregulation of miR-183 expression. Further investigation revealed that the novel hair cells produced, induced by DAPT, were derived from transdifferentiated supporting cells. Additionally, myosin VI-positive hair cell numbers were increased by Notch signaling inhibition in in vitro experiments with cultured neonatal mouse inner ear precursor cells. This effect was reversed by miR-183 inhibition. These findings indicate that the Notch signaling pathway served a repressing role during the regeneration of hair cells. Inhibiting this signal improved hair cell regeneration in the gentamicin-damaged cochlear model. miR-183 was demonstrated to be involved in hair cell differentiation and regeneration, and was required for the differentiation of the Notch-inhibited hair cells.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
56.9
作者：
RYALS, BM;RUBEL, EW
通讯作者：
RUBEL, EW
影响因子：
56.9
作者：
CORWIN, JT;COTANCHE, DA
通讯作者：
COTANCHE, DA
HES5在产后和成年小鼠内耳以及药物受损的耳蜗中的表达。
DOI：
10.1007/s10162-009-0162-2
发表时间：
2009-09
影响因子：
2.4
作者：
Hartman, Byron H.;Basak, Onur;Nelson, Branden R.;Taylor, Verdon;Bermingham-McDonogh, Olivia;Reh, Thomas A.
通讯作者：
Reh, Thomas A.
影响因子：
2.5
作者：
Weston, Michael D.;Pierce, Marsha L.;Jensen-Smith, Heather C.;Fritzsch, Bernd;Rocha-Sanchez, Sonia;Beisel, Kirk W.;Soukup, Garrett A.
通讯作者：
Soukup, Garrett A.