Epithelial-Mesenchymal Transition Participates in the Formation of Vestibular Flat Epithelium.
Epithelial-Mesenchymal Transition Participates in the Formation of Vestibular Flat Epithelium.
复制标题
上皮-间质转化参与前庭扁平上皮的形成
DOI：
10.3389/fnmol.2021.809878
复制
发表时间：
2021
影响因子：
4.8
通讯作者：
Gong SS
中科院分区：
文献类型：
--
作者：
He L;Wang GP;Guo JY;Chen ZR;Liu K;Gong SS
人和小鼠的前庭感觉上皮在严重损伤后可能退化为一层扁平细胞，称为扁平上皮（FE）。然而，前庭扁平上皮的发病机制仍不清楚。为了确定上皮 - 间质转化（EMT）是否参与前庭扁平上皮的形成，我们使用了一种成熟的小鼠模型，通过向内耳注射链霉素诱导椭圆囊中的扁平上皮形成。利用免疫荧光染色和定量逆转录聚合酶链反应（qRT - PCR）检测间质和上皮细胞标志物以及细胞增殖情况。通过转录组微阵列分析评估EMT的功能。结果表明，与正常椭圆囊相比，前庭扁平上皮中间质细胞标志物（α - SMA、S100A4、波形蛋白和Fn1）上调。在扁平上皮形成过程中观察到正常状态下不存在的活跃细胞增殖。微阵列分析确定了前庭扁平上皮中1227个上调基因和962个下调基因。基因本体论（GO）分析显示，差异表达基因（DEGs）与几个与EMT相关的GO术语高度相关，例如细胞黏附、细胞迁移和细胞外基质。通路富集分析显示，差异表达基因富集在与EMT相关的信号通路中，包括细胞外基质（ECM） - 受体相互作用、黏着斑、PI3K/Akt信号通路和细胞黏附分子。蛋白质 - 蛋白质相互作用网络筛选出20个枢纽基因，分别是Akt、Casp3、Col1a1、Col1a2、Fn1、Hgf、Igf1、Il1b、Irs1、Itga2、Itga5、Jun、Mapk1、Myc、Nras、Pdgfrb、Tgfb1、Thbs1、Trp53和Col2a1。据报道，这些基因中的大多数参与了各种组织中的EMT过程。使用qRT - PCR验证了枢纽基因的mRNA表达水平。总之，本研究表明EMT在前庭扁平上皮的形成中起重要作用，并提供了前庭扁平上皮转录组特征的概况。
The vestibular sensory epithelium of humans and mice may degenerate into a layer of flat cells, known as flat epithelium (FE), after a severe lesion. However, the pathogenesis of vestibular FE remains unclear. To determine whether the epithelial–mesenchymal transition (EMT) participates in the formation of vestibular FE, we used a well-established mouse model in which FE was induced in the utricle by an injection of streptomycin into the inner ear. The mesenchymal and epithelial cell markers and cell proliferation were examined using immunofluorescence staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The function of the EMT was assessed through transcriptome microarray analysis. The results demonstrated that mesenchymal cell markers (α-SMA, S100A4, vimentin, and Fn1) were upregulated in vestibular FE compared with the normal utricle. Robust cell proliferation, which was absent in the normal status, was observed in the formation of FE. Microarray analysis identified 1,227 upregulated and 962 downregulated genes in vestibular FE. Gene Ontology (GO) analysis revealed that differentially expressed genes (DEGs) were highly associated with several EMT-related GO terms, such as cell adhesion, cell migration, and extracellular matrix. Pathway enrichment analysis revealed that DEGs were enriched in the EMT-related signaling pathways, including extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/Akt signaling pathway and cell adhesion molecule. Protein–protein interaction networks screened 20 hub genes, which were Akt, Casp3, Col1a1, Col1a2, Fn1, Hgf, Igf1,Il1b, Irs1, Itga2, Itga5, Jun, Mapk1, Myc, Nras, Pdgfrb, Tgfb1, Thbs1, Trp53, and Col2a1. Most of these genes are reportedly involved in the EMT process in various tissues. The mRNA expression level of hub genes was validated using qRT-PCR. In conclusion, the present study indicates that EMT plays a significant role in the formation of vestibular FE and provides an overview of transcriptome characteristics in vestibular FE.
登录
查看更多内容
DOI：
10.1002/dvdy.24561
发表时间：
2018-03
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Haensel D;Dai X
通讯作者：
Dai X
影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
Medici D
影响因子：
5.3
作者：
Fu X;Wan P;Li P;Wang J;Guo S;Zhang Y;An Y;Ye C;Liu Z;Gao J;Yang J;Fan J;Chai R
通讯作者：
Chai R
影响因子：
12.4
作者：
Isgrig, Kevin;Shteamer, Jack W.;Chien, Wade W.
通讯作者：
Chien, Wade W.
影响因子：
--
作者：
Jayachandran A;Anaka M;Prithviraj P;Hudson C;McKeown SJ;Lo PH;Vella LJ;Goding CR;Cebon J;Behren A
通讯作者：
Behren A