ADAM10 promotes the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway.
ADAM10 promotes the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway.
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ADAM10通过激活PI3K/AKT通路促进黄韧带细胞增殖
DOI：
10.3892/ijmm.2020.4809
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发表时间：
2021-03
影响因子：
5.4
通讯作者：
Guo K
中科院分区：
文献类型：
--
作者：
Pan B;Huo T;Cao M;Jing L;Luo X;Qu Z;Feng H;Yuan F;Guo K
黄韧带肥厚是导致椎管狭窄和后纵韧带骨化的重要原因。虽然许多研究都集中在LFH的机制，细胞机制仍然知之甚少。本研究旨在探讨LFH中差异表达基因（DEG）的作用，阐明LFH的发病机制，为LFH的进一步研究提供潜在的治疗靶点。GSE 113212数据集从Gene Expression Omnibus（GEO）数据库下载。分析芯片数据，获得DEG。采用基因本体论（GO）、京都基因与基因组百科全书（KEGG）富集和蛋白质相互作用（PPI）网络分析等生物信息学方法，获得关键基因和信号通路。此外，对肥大黄韧带细胞进行体外培养，通过体外细胞生物学和分子生物学实验，鉴定黄韧带细胞中的关键基因和信号通路。共筛选出2，123个基因作为DEG。在这些DEG中，1，384个基因上调，739个基因下调。KEGG途径分析显示DEG主要富集在PI 3 K/AKT信号通路中，PPI网络分析筛选出A去整合素和金属蛋白酶10（ADAM 10）为关键基因。体外实验验证表明，ADAM 10通过激活PI 3 K/AKT通路促进黄韧带细胞增殖，导致黄韧带肥大。体外实验结果提示，ADAM 10通过激活PI 3 K/AKT通路促进黄韧带细胞增殖，可能是LFH的发病机制之一。本研究结果为进一步研究LFH的细胞机制提供了基础和方向，并为LFH的治疗提供了新的靶点和临床途径。
Ligamentum flavum hypertrophy (LFH) is an important cause of spinal canal stenosis and posterior longitudinal ligament ossification. Although a number of studies have focused on the mechanisms responsible for LFH, the cellular mechanisms remain poorly understood. The aim of the present study was to investigate the roles of differentially expressed genes (DEGs) in LFH, elucidate the mechanisms responsible for LFH and provide a potential therapeutic target for further studies. The GSE113212 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The microarray data were analyzed and DEGs were obtained. Bioinformatics methods, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein-protein interaction (PPI) network analyses were used to obtain the key genes and signaling pathways. In addition, cells derived from hypertrophied ligamentum flavum were cultured, and the key genes and signaling pathways in ligamentum cells were identified through in vitro cell biology and molecular biology experiments. A total of 2,123 genes were screened as DEGs. Among these DEGs, 1,384 genes were upregulated and 739 genes were downregulated. The KEGG pathway analysis revealed that the DEGs were mainly enriched in the PI3K/AKT signaling pathway, and the PPI network analysis screened A disintegrin and metalloproteinase 10 (ADAM10) as a key gene. In vitro experimental verification revealed that ADAM10 promoted the proliferation of ligamentum flavum cells and led to the hypertrophy of the ligamentum by activating the PI3K/AKT pathway. On the whole, the in vitro experimental results suggested that ADAM10 promoted the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway, which may represent a pathogenic mechanism of LFH. The findings of the present study may provide a basis and direction for further studies on the cellular mechanisms of LFH and present a potential novel therapeutic target and clinical approach.
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影响因子：
82.9
作者：
Lagares D;Ghassemi-Kakroodi P;Tremblay C;Santos A;Probst CK;Franklin A;Santos DM;Grasberger P;Ahluwalia N;Montesi SB;Shea BS;Black KE;Knipe R;Blati M;Baron M;Wu B;Fahmi H;Gandhi R;Pardo A;Selman M;Wu J;Pelletier JP;Martel-Pelletier J;Tager AM;Kapoor M
通讯作者：
Kapoor M
影响因子：
5.2
作者：
Matsuoka T;Yashiro M
通讯作者：
Yashiro M
DOI：
10.1073/pnas.0500918102
发表时间：
2005-06-28
影响因子：
11.1
作者：
Maretzky, T;Reiss, K;Saftig, P
通讯作者：
Saftig, P
影响因子：
6.4
作者：
Chueh, Hee Won;Park, Seong Kook;Bae, Woo Yong
通讯作者：
Bae, Woo Yong
影响因子：
3.4
作者：
Liu, Songyang;Zhang, Wei;Wang, Guangyi
通讯作者：
Wang, Guangyi