Search | Engineering

订阅投稿

首页工程期刊工程焦点工程成就工程前沿关于我们 English

资源类型

期刊论文 5

年份

2022 1

2019 2

2016 2

关键词

检索范围：

排序：展示方式：

Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium

null

《医学前沿（英文）》 2016年第10卷第3期页码 330-335 doi: 10.1007/s11684-016-0459-6

摘要：

The enhancer of zeste 2 polycomb repressive complex 2 subunit (Ezh2) is a histone-lysine N-methyltransferase enzyme that participates in DNA methylation. Ezh2 has also been reported to play crucial roles in stem cell proliferation and differentiation. However, the detailed expression profile of Ezh2 during mouse cochlear development has not been investigated. Here, we examined the spatiotemporal expression of Ezh2 in the cochlea during embryonic and postnatal development. Ezh2 expression began to be observed in the whole otocyst nuclei at embryonic day 9.5 (E9.5). At E12.5, Ezh2 was expressed in the nuclei of the cochlear prosensory epithelium. At E13.5 and E15.5, Ezh2 was expressed from the apical to the basal turns in the nuclei of the differentiating cochlear epithelium. At postnatal day (P) 0 and 7, the Ezh2 expression was located in the nuclei of the cochlear epithelium in all three turns and could be clearly seen in outer and inner hair cells, supporting cells, the stria vascularis, and spiral ganglion cells. Ezh2 continued to be expressed in the cochlear epithelium of adult mice. Our results provide the basic Ezh2 expression pattern and might be useful for further investigating the detailed role of Ezh2 during cochlear development.

关键词： polycomb repressive complex Ezh2 expression inner ear cochlea development

HTML PDF 收藏

Apigenin alleviates neomycin-induced oxidative damage via the Nrf2 signaling pathway in cochlear hair

《医学前沿（英文）》 2022年第16卷第4期页码 637-650 doi: 10.1007/s11684-021-0864-3

摘要： Oxidative stress plays an important role in the pathogenesis of aminoglycoside-induced hearing loss and represents a promising target for treatment. We tested the potential effect of apigenin, a natural flavonoid with anticancer, anti-inflammatory, and antioxidant activities, on neomycin-induced ototoxicity in cochlear hair cells in vitro. Results showed that apigenin significantly ameliorated the loss of hair cells and the accumulation of reactive oxygen species upon neomycin injury. Further evidence suggested that the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was activated by apigenin treatment. Disruption of the Nrf2 axis abolished the effects of apigenin on the alleviation of oxidative stress and subsequent apoptosis of hair cells. This study provided evidence of the protective effect of apigenin on cochlear hair cells and its underlying mechanism.

关键词： apigenin aminoglycosides ototoxicity oxidative stress Nrf2 signaling pathway

HTML PDF 收藏

Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice

null

《医学前沿（英文）》 2016年第10卷第4期页码 481-489 doi: 10.1007/s11684-016-0494-3

摘要：

The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice (LKB1^Pax2 CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1^Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1^Pax2 CKO mice were clustered and misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles resulting from abnormal migration of kinocilium was observed in the mutant mice. The orientation of stereociliary bundles and the migration of kinocilia are critical indicators of planar cell polarity (PCP) of hair cells. LKB1 deficiency in LKB1^Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic development. Our results suggest that LKB1 is required in PCP formation in cochlear hair cells in mice.

关键词： LKB1 stereociliary bundles kinocilium planar cell polarity hearing mice

HTML PDF 收藏

is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice

Yuqin Men, Xiujuan Li, Hailong Tu, Aizhen Zhang, Xiaolong Fu, Zhishuo Wang, Yecheng Jin, Congzhe Hou, Tingting Zhang, Sen Zhang, Yichen Zhou, Boqin Li, Jianfeng Li, Xiaoyang Sun, Haibo Wang, Jiangang Gao

《医学前沿（英文）》 2019年第13卷第6期页码 690-704 doi: 10.1007/s11684-018-0638-8

摘要： encodes the taperin protein, which is concentrated in the tapered region of hair cell stereocilia in the inner ear. In humans, mutations cause autosomal recessive nonsyndromic deafness (DFNB79) by an unknown mechanism. To determine the role of in hearing, we generated -null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background. We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells of -null mice starting from postnatal day 30. Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts. The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings. Radixin, a protein expressed at stereocilia tapering, was abnormally dispersed along the stereocilia shafts in null mice. The expression levels of radixin and -actin significantly decreased. We propose that is critical to the retention of the integrity of the stereociliary rootlet. Loss of in -null mice caused the disruption of the stereociliary rootlet, which resulted in damage to stereociliary bundles and hearing impairments. The generated -null mice are ideal models of human hereditary deafness DFNB79.

关键词： TPRN stereocilia stereociliary rootlet actin filament CRISPR/Cas9 hearing

HTML PDF 收藏

Unidirectional and stage-dependent roles of Notch1 in Wnt-responsive Lgr5

Hui Jiang, Shan Zeng, Wenli Ni, Yan Chen, Wenyan Li

《医学前沿（英文）》 2019年第13卷第6期页码 705-712 doi: 10.1007/s11684-019-0703-y

摘要： Wnt and Notch signaling play crucial roles in the determination of the prosensory domain and in the differentiation of hair cells (HCs) and supporting cells during mouse inner ear development; however, the relationship between the two signaling pathways in the mouse cochlea remains largely unknown. Here, we investigated the interactions between Notch and Wnt signaling on the basis of the bidirectional regulation of Notch1 specifically in Wnt-responsive Lgr5 progenitors during different cochlear development stages. We found that the downregulation of Notch1 in Lgr5 cells from embryonic day (E) 14.5 to E18.5 can drive the quiescent Lgr5 cells to re-enter the cell cycle and differentiate into extra HCs, whereas the upregulation of Notch1 expression did not affect the proliferation or differentiation of otic progenitor cells. No effect was observed on the upregulation or downregulation of Notch1 in Lgr5 cells from E10.5 to E14.5. We concluded that the roles of Notch1 in Wnt-responsive Lgr5 cells are unidirectional and stage dependent and Notch1 serves as a negative regulator for Lgr5 progenitor activation during cochlear differentiation. Our findings improved the understanding of the interactions between Notch and Wnt signaling in cochlear development.

关键词： inner ear cochlear Wnt Notch Lgr5 auditory system