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Transcriptome analysis reveals dysregulation of genes involved in oxidative phosphorylation in a murine model of retinopathy of prematurity
Pediatric Research ( IF 3.6 ) Pub Date : 2020-02-13 , DOI: 10.1038/s41390-020-0793-x
Magdalena Zasada 1 , Anna Madetko-Talowska 2 , Cecilie Revhaug 3, 4 , Anne Gro W Rognlien 3, 4 , Lars O Baumbusch 3 , Teofila Książek 2 , Katarzyna Szewczyk 2 , Agnieszka Grabowska 2 , Miroslaw Bik-Multanowski 2 , Jacek Józef Pietrzyk 1 , Przemko Kwinta 1 , Ola Didrik Saugstad 3, 4
Affiliation  

Background Retinal gene expression pattern is severely altered after exposition to hyperoxia in mice with oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity. Gene ontology and signaling pathway analyses may add new insights into a better understanding of the pathogenesis of this disease. Methods Seven-day-old C57BL/6J mice ( n = 60) were exposed to 75% oxygen for 5 days and then recovered in room air. The controls ( n = 60) were kept in the normoxic conditions. Retinas were harvested immediately following hyperoxia, during the phase of maximal neovascularization, and at the time of neovascularization regression. The retinal RNA samples were evaluated for gene expression using mouse gene expression microarrays. DAVID annotation tools were used for gene ontology and pathway analyses. Results The most significantly enriched signaling pathways during the neovascularization phase of OIR were: focal adhesion; ECM–receptor interaction; PI3K-Akt; oxidative phosphorylation; and Alzheimer’s, Parkinson’s and Huntington’s disease signaling pathways. Genes involved in apoptosis, cell proliferation, cell differentiation, and immune responses were associated with neovascularization regression. Conclusions Performed analyses revealed the possible involvement of various signaling pathways in OIR pathomechanism, mostly specific to the OIR phase. Dysregulation of genes involved in oxidative phosphorylation may have an impact on neovascularization development.

中文翻译:

转录组分析揭示了早产儿视网膜病变小鼠模型中氧化磷酸化相关基因的失调

背景 患有氧诱导性视网膜病变 (OIR)(一种常见的早产儿视网膜病变模型)的小鼠在暴露于高氧后,视网膜基因表达模式发生了严重改变。基因本体论和信号通路分析可能会为更好地了解这种疾病的发病机制提供新的见解。方法 将 7 天大的 C57BL/6J 小鼠(n = 60)暴露于 75% 的氧气中 5 天,然后在室内空气中恢复。对照 (n = 60) 保持在常氧条件下。在高氧后、最大新生血管形成阶段和新生血管形成消退时立即收获视网膜。使用小鼠基因表达微阵列评估视网膜 RNA 样本的基因表达。DAVID 注释工具用于基因本体和通路分析。结果 OIR新生血管形成期最显着富集的信号通路是:粘着斑;ECM-受体相互作用;PI3K-Akt; 氧化磷酸化;和阿尔茨海默病、帕金森病和亨廷顿病信号通路。参与细胞凋亡、细胞增殖、细胞分化和免疫反应的基因与新血管形成消退有关。结论 进行的分析揭示了 OIR 病理机制中可能涉及各种信号通路,主要针对 OIR 阶段。参与氧化磷酸化的基因的失调可能对新血管形成产生影响。帕金森病和亨廷顿病信号通路。参与细胞凋亡、细胞增殖、细胞分化和免疫反应的基因与新血管形成消退有关。结论 进行的分析揭示了 OIR 病理机制中可能涉及各种信号通路,主要针对 OIR 阶段。参与氧化磷酸化的基因的失调可能对新血管形成的发展产生影响。帕金森病和亨廷顿病信号通路。参与细胞凋亡、细胞增殖、细胞分化和免疫反应的基因与新血管形成消退有关。结论 进行的分析揭示了 OIR 病理机制中可能涉及各种信号通路,主要针对 OIR 阶段。参与氧化磷酸化的基因的失调可能对新血管形成产生影响。
更新日期:2020-02-13
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