Yu Fang-Fang, Zhang Yan-Xiang, Zhang Lian-He, Li Wen-Rong, Guo Xiong, Lammi Mikko J
Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi'an Jiaotong University, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an Department of Orthopedics, Baoji People's Hospital, Baoji, China Department of Integrative Medical Biology, University of Umeå, Umeå, Sweden.
Medicine (Baltimore). 2016 Dec;95(52):e5669. doi: 10.1097/MD.0000000000005669.
As environmental risk factors (ERFs) play an important role in the pathogenesis of Kashin-Beck disease (KBD), it is important to identify the interaction between ERFs and differentially expression genes (DEGs) in KBD. The environmental response genes (ERGs) were analyzed in cartilage of KBD in comparison to normal controls.We searched 5 English and 3 Chinese databases from inception to September 2015, to identify case-control studies that examined ERFs for KBD using integrative meta-analysis and systematic review. Total RNA was isolated from articular cartilage of KBD patients and healthy controls. Human whole genome microarray chip (Agilent) was used to analyze the amplified, labeled, and hybridized total RNA, and the validated microarray data were partially verified using real-time quantitative polymerase chain reaction (qRT-PCR). The ERGs were derived from the Comparative Toxicogenomics Database. The identified ERGs were subjected to KEGG pathway enrichment, biological process (BP), and interaction network analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.7, and STRING.The trace elements (selenium and iodine), vitamin E, and polluted grains (T-2 toxin/HT-2 toxin, deoxynivalenol, and nivalenol) were identified as the ERFs for KBD using meta-analysis and review. We identified 21 upregulated ERGs and 7 downregulated ERGs in cartilage with KBD compared with healthy controls, which involved in apoptosis, metabolism, and growth and development. KEGG pathway enrichment analysis found that 2 significant pathways were involved with PI3K-Akt signaling pathway and P53 signaling pathway, and gene ontology function analysis found 3 BPs involved with apoptosis, death, and cell death in KBD cartilage.According to previous results and our own research, we suggest that the trace element selenium and vitamin E induce PI3K-Akt signaling pathway and the mycotoxins (T-2 toxin/HT-2 toxin and DON) induce P53 signaling pathway, contributing to the development of KBD, and chondrocyte apoptosis and cell death.
由于环境危险因素（ERFs）在大骨节病（KBD）的发病机制中起重要作用，因此识别KBD中ERFs与差异表达基因（DEGs）之间的相互作用很重要。与正常对照相比，分析了KBD软骨中的环境反应基因（ERGs）。我们检索了从建库至2015年9月的5个英文数据库和3个中文数据库，以通过整合荟萃分析和系统评价来识别检测KBD的ERFs的病例对照研究。从KBD患者和健康对照的关节软骨中分离总RNA。使用人类全基因组微阵列芯片（安捷伦）分析扩增、标记和杂交后的总RNA，并使用实时定量聚合酶链反应（qRT-PCR）对经过验证的微阵列数据进行部分验证。ERGs来自比较毒理基因组学数据库。使用注释、可视化和综合发现数据库（DAVID）v6.7和STRING对鉴定出的ERGs进行KEGG通路富集、生物学过程（BP）和相互作用网络分析。通过荟萃分析和综述，确定微量元素（硒和碘）、维生素E以及污染谷物（T-2毒素/HT-2毒素、脱氧雪腐镰刀菌烯醇和雪腐镰刀菌烯醇）为KBD的ERFs。与健康对照相比，我们在KBD软骨中鉴定出21个上调的ERGs和7个下调的ERGs，它们参与细胞凋亡、代谢以及生长和发育。KEGG通路富集分析发现2条重要通路与PI3K-Akt信号通路和P53信号通路有关，基因本体功能分析发现3个BP与KBD软骨中的细胞凋亡、死亡和细胞死亡有关。根据先前的结果和我们自己的研究，我们认为微量元素硒和维生素E诱导PI3K-Akt信号通路，而霉菌毒素（T-2毒素/HT-2毒素和DON）诱导P53信号通路，这有助于KBD的发展以及软骨细胞凋亡和细胞死亡。
