Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells.

IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Organogenesis Pub Date : 2018-01-01 Epub Date: 2018-06-14 DOI:10.1080/15476278.2018.1462433
Zhao Han, Yu-Yan Gu, Ning Cong, Rui Ma, Fang-Lu Chi
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引用次数: 6

Abstract

We aimed to investigate the beneficial effect of Celastrol on inner ear stem cells and potential therapeutic value for hearing loss. The inner ear stem cells were isolated and characterized from utricular sensory epithelium of adult mice. The stemness was evaluated by sphere formation assay. The relative expressions of Atoh1, MAP-2 and Myosin VI were measured by RT-PCR and immunoblotting. The up-regulation of MAP-2 was also analysed with immunofluorescence. The in vitro neuronal excitability was interrogated by calcium oscillation. The electrophysiological property was determined by inward current recorded on patch clamp. Our results demonstrated that Celastrol treatment significantly improved the viability and proliferation of mouse inner ear stem cells, and facilitated sphere formation. Moreover, Celastrol stimulated differentiation of mouse inner ear stem cells to neuronal-like cells and enhanced neural excitability. Celastrol also enhanced neuronal-like cell identity in the inner ear stem cell derived neurons, as well as their electrophysiological function. Most notably, these effects were apparently associated with the upregulation of Atoh1 in response to Celastrol treatment. Celastrol showed beneficial effect on inner ear stem cells and held therapeutic promise against hearing loss.

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Celastrol增强内耳干细胞中Atoh1的表达,促进其向功能性听觉神经元样细胞分化。
我们旨在探讨雷公藤红素对内耳干细胞的有益作用及其对听力损失的潜在治疗价值。从成年小鼠耳室感觉上皮中分离并鉴定了内耳干细胞。用成球法评价茎干性。RT-PCR和免疫印迹法检测Atoh1、MAP-2和Myosin VI的相对表达量。用免疫荧光分析MAP-2的上调。用钙振荡法研究体外神经元的兴奋性。通过膜片钳记录向内电流来测定其电生理特性。我们的研究结果表明,Celastrol处理显著提高了小鼠内耳干细胞的活力和增殖,并促进了球体的形成。此外,雷公藤红素刺激小鼠内耳干细胞向神经元样细胞分化,增强神经兴奋性。雷公藤红素还增强了内耳干细胞衍生神经元的神经元样细胞特性,以及它们的电生理功能。最值得注意的是,这些效果显然与Celastrol治疗后Atoh1的上调有关。Celastrol显示出对内耳干细胞的有益作用,并对治疗听力损失具有前景。
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来源期刊
Organogenesis
Organogenesis BIOCHEMISTRY & MOLECULAR BIOLOGY-DEVELOPMENTAL BIOLOGY
CiteScore
4.10
自引率
4.30%
发文量
6
审稿时长
>12 weeks
期刊介绍: Organogenesis is a peer-reviewed journal, available in print and online, that publishes significant advances on all aspects of organ development. The journal covers organogenesis in all multi-cellular organisms and also includes research into tissue engineering, artificial organs and organ substitutes. The overriding criteria for publication in Organogenesis are originality, scientific merit and general interest. The audience of the journal consists primarily of researchers and advanced students of anatomy, developmental biology and tissue engineering. The emphasis of the journal is on experimental papers (full-length and brief communications), but it will also publish reviews, hypotheses and commentaries. The Editors encourage the submission of addenda, which are essentially auto-commentaries on significant research recently published elsewhere with additional insights, new interpretations or speculations on a relevant topic. If you have interesting data or an original hypothesis about organ development or artificial organs, please send a pre-submission inquiry to the Editor-in-Chief. You will normally receive a reply within days. All manuscripts will be subjected to peer review, and accepted manuscripts will be posted to the electronic site of the journal immediately and will appear in print at the earliest opportunity thereafter.
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