关于ceRNA调节昼夜节律对胆道新血管化的观点
Ying Yang1,2, Shu Su1, Jia Chen1
1Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Scientific reports
|November 9, 2024
概括
扰乱小鼠的昼夜时钟通过改变与伤口愈合相关的基因表达来促进胆道新血管化 (CNV). 这项研究强调了光暗周期对眼睛疾病机制的影响.
科学领域:
- 眼科和视觉科学 眼科和视觉科学
- 时间生物学 时间生物学
- 分子生物学分子生物学
背景情况:
- 状新血管化 (CNV) 是与年龄相关的黄斑变性 (AMD) 的关键因素,导致视力丧失.
- 视网膜的昼夜钟调节视觉功能,其干扰越来越多地与眼睛疾病有关.
- 昼夜节律扰乱与中枢神经病毒病原体之间的确切关系尚不清楚.
研究的目的:
- 在中断的光暗周期下,研究 CNV 中竞争的内源性 RNA (ceRNA) 网络的调节机制.
- 为了确定关键的基因和途径,涉及到由昼夜节律变化影响的CNV发展.
主要方法:
- 在受控和时差 (循环节障碍) 条件下建立了激光诱导的CNV小鼠模型.
- 进行全转录组测序 (RNA-seq) 来识别差异表达基因 (DEG),miRNA,lncRNA和circRNA.
- 利用了基因本体学 (GO) 分析,基因组丰富分析 (GSEA),权重基因同表达网络分析 (WGCNA) 和ceRNA网络构建.
主要成果:
- 确定了661个DEG,31个差异表达的miRNA,106个lncRNA和87个circRNA.
- 上调的DEGs主要与生殖系统的发展有关,而ceRNA网络目标与伤口愈合和上皮形态发生有关.
- WGCNA确定了模块特定的枢纽基因,并通过qPCR验证了十个关键基因,证实了它们的改变表达模式.
结论:
- 循环节律的扰乱显著影响视网膜中的基因表达特征,促进 CNV 所涉及的途径.
- ceRNA网络在调解光暗周期改变对 CNV 的影响方面发挥着至关重要的作用.
- 已识别的关键基因和通路为管理CNV和相关视力丧失提供了潜在的治疗点.
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