通过计算机分析识别肺高血压中Zip8相关的枢纽基因
FanRong Zhao1,2,3, Yujing Chen1,2,3, Yuliang Xie1,2,3
1College of Pharmacy, Xinxiang Medical University, Xinxiang, China.
PeerJ
|September 4, 2023
概括
载体ZIP8 (SLC39A8) 在肺高血压 (PH) 中是下调的. 这项研究确定了与ZIP8相关的代谢基因,为PH病原体和这种严重肺部疾病的潜在治疗点提供了新的见解.
科学领域:
- 肺血管疾病研究研究
- 分子生物学和遗传学 分子生物学和遗传学
- 生物信息学和系统生物学
背景情况:
- 肺高血压 (PH) 是一种严重的疾病,其特征是肺血管重塑,导致右心力衰竭.
- 类似Zrt/Irt的蛋白8 (ZIP8),一种由SLC39A8编码的金属离子载体,在肺微血管内皮中发现.
- 在PH的发展和进展中ZIP8的具体作用在很大程度上仍未被定义.
研究的目的:
- 为了研究SLC39A8在肺高血压中的表达模式.
- 在PH中识别与SLC39A8相关的基因和代谢途径.
- 探索ZIP8及其相关代谢基因在PH病原发生中的潜在作用.
主要方法:
- 对公共基因表达数据集 (GSE24988,GSE113439,GSE117261,GSE15197) 的生物信息学分析,以确定SLC39A8表达和差异表达基因 (DEG).
- 基因组丰富分析 (GSEA) 用于确定丰富的信号通路.
- 细胞图和cytoHubba分析以确定枢纽基因.
- 使用逆转录酶-聚合酶链反应在PH (SU5416 / 缺氧) 的小鼠模型中验证基因表达.
主要成果:
- 在PH患者中,SLC39A8表达显著下调,并在PH小鼠肺组织中得到验证.
- 与SLC39A8相关的基因主要在代谢途径中得到丰富.
- 确定了7个与SLC39A8相关的代谢枢纽基因,其中4个 (Fasn, Nsdhl, Acat2, Acly) 在PH小鼠中显示下调,涉及脂肪酸和胆固醇代谢.
结论:
- ZIP8 (SLC39A8) 在肺高血压下调节,这表明它具有保护作用.
- 与ZIP8相关的代谢基因,特别是那些参与脂肪酸和胆固醇合成/代谢的基因,在PH中失调.
- 这些发现为PH的分子机制提供了新的见解,并突出了ZIP8和相关的代谢途径作为潜在的治疗点.
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