Tlr2/4 Double Knockout Attenuates the Degeneration of Primary Auditory Neurons: Potential Mechanisms From Transcriptomic Perspectives.
Tlr2/4 Double Knockout Attenuates the Degeneration of Primary Auditory Neurons: Potential Mechanisms From Transcriptomic Perspectives.
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Tlr2/4 双敲除减轻初级听觉神经元的退化：转录组学角度的潜在机制
DOI：
10.3389/fcell.2021.750271
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发表时间：
2021
影响因子：
5.5
通讯作者：
Xiang M
中科院分区：
文献类型：
--
作者：
Wang Q;Shen Y;Pan Y;Chen K;Ding R;Zou T;Zhang A;Guo D;Ji P;Fan C;Mei L;Hu H;Ye B;Xiang M
原发性听觉神经元变性（PAND）小鼠的转录组图显示了其发病的关键途径，包括补体级联、免疫反应、肿瘤坏死因子（TNF）信号通路和细胞因子-细胞因子受体相互作用。toll样受体（TLRs）是重要的免疫和炎症分子，已被证明可以破坏PAND的疾病网络。在卡那霉素联合速尿破坏耳蜗毛细胞的PAND模型中，Tlr 2/4双敲除（DKO）小鼠具有听觉保存优势，主要表现在4-16 kHz。DKO组和野生型（WT）小鼠在第30天耳蜗毛细胞完全受损，但DKO组罗森thal管螺旋神经节神经元（SGN）密度显著高于WT组。p38和p65的免疫组化结果显示，DKO小鼠SGN变性的衰减可能不是由典型Tlr信号通路介导的。DKO和WT小鼠的SGN转录组表明，它们的不同转录组与SGN变性转录组之间存在反向基因集富集关系，这与形态学结果一致。核心模块分析提示DKO小鼠可能通过激活两个簇来调节SGN变性，涉及的分子包括EGF、STAT3、CALB2、LOX、SNAP25、CAV2、SDC4、MYL1、NCS1、PVALB、TPM4和TMOD4。
The transcriptomic landscape of mice with primary auditory neurons degeneration (PAND) indicates key pathways in its pathogenesis, including complement cascades, immune responses, tumor necrosis factor (TNF) signaling pathway, and cytokine-cytokine receptor interaction. Toll-like receptors (TLRs) are important immune and inflammatory molecules that have been shown to disrupt the disease network of PAND. In a PAND model involving administration of kanamycin combined with furosemide to destroy cochlear hair cells, Tlr 2/4 double knockout (DKO) mice had auditory preservation advantages, which were mainly manifested at 4–16 kHz. DKO mice and wild type (WT) mice had completely damaged cochlear hair cells on the 30th day, but the density of spiral ganglion neurons (SGN) in the Rosenthal canal was significantly higher in the DKO group than in the WT group. The results of immunohistochemistry for p38 and p65 showed that the attenuation of SGN degeneration in DKO mice may not be mediated by canonical Tlr signaling pathways. The SGN transcriptome of DKO and WT mice indicated that there was an inverted gene set enrichment relationship between their different transcriptomes and the SGN degeneration transcriptome, which is consistent with the morphology results. Core module analysis suggested that DKO mice may modulate SGN degeneration by activating two clusters, and the involved molecules include EGF, STAT3, CALB2, LOX, SNAP25, CAV2, SDC4, MYL1, NCS1, PVALB, TPM4, and TMOD4.
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影响因子：
5.7
作者：
De Paola, Massimiliano;Mariani, Alessandro;Fanelli, Roberto
通讯作者：
Fanelli, Roberto
影响因子：
3.7
作者：
Gao K;Ding D;Sun H;Roth J;Salvi R
通讯作者：
Salvi R
DOI：
10.1126/science.1241062
发表时间：
2014-05-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Géléoc GS;Holt JR
通讯作者：
Holt JR
小鼠耳蜗 Sox2 支持细胞中与年龄相关的转录组变化。
影响因子：
7.5
作者：
Cheng, Cheng;Wang, Yunfeng;Chai, Renjie
通讯作者：
Chai, Renjie
影响因子：
5.1
作者：
Fu, Xiaolong;An, Yachun;Chai, Renjie
通讯作者：
Chai, Renjie