Differential gene and lncRNA expression in the lower thoracic spinal cord following ischemia/reperfusion-induced acute kidney injury in rats.

Differential gene and lncRNA expression in the lower thoracic spinal cord following ischemia/reperfusion-induced acute kidney injury in rats.
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大鼠缺血/再灌注急性肾损伤后下胸段脊髓差异基因和lncRNA表达

DOI:
10.18632/oncotarget.18584
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发表时间:
2017-08-08
期刊:
影响因子:
--
通讯作者:
Lv YM
Lv YM
中科院分区:
其他
文献类型:
--
作者:
Liu QQ;Liu H;He ZG;Zhang SJ;Liu BW;Wang L;Qiu WH;Xu Q;Xiang HB;Lv YM

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我们使用高通量RNA测序分析大鼠缺血/再灌注(I/R)诱导的急性肾损伤(阿基)过程中下胸脊髓中差异基因和lncRNA表达模式。我们观察到,在32662个mRNA中,4296个在I/R诱导的阿基时在脊髓的T8-12节段中差异表达。其中,62个上调,34个下调,以响应I/R(FDR < 0.05,|log 2光纤通道|> 1)。此外,在3849个lncRNA转录物中鉴定出52个差异表达的lncRNA(35个上调和17个下调)。通过基因本体富集分析,将差异表达的mRNA分别标注为“生物学过程”、“细胞成分”和“分子功能”。KEGG途径富集分析显示,I/R后细胞周期和肾素-血管紧张素途径上调,而蛋白质消化和吸收、hedgehog、神经营养因子、MAPK和PI 3 K-Akt信号转导下调。通过选择的mRNA和lncRNA的qRT-PCR和蛋白质印迹分析验证RNA-seq数据。我们观察到,Bax,Caspase-3和磷酸化AKT上调和Bcl-2下调,在脊髓中响应肾损伤。我们还发现三种lncRNA(TCONS_00042175,TCONS_00058568和TCONS_00047728)与肾损伤程度呈负相关。这些发现为I/R诱导的大鼠阿基后下胸脊髓中lncRNA和mRNA的差异表达提供了证据,并提示了潜在的临床适用性。
We used high-throughput RNA sequencing to analyze differential gene and lncRNA expression patterns in the lower thoracic spinal cord during ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) in rats. We observed that of 32662 mRNAs, 4296 out were differentially expressed in the T8-12 segments of the spinal cord upon I/R-induced AKI. Among these, 62 were upregulated and 34 were downregulated in response to I/R (FDR < 0.05, |log2FC| > 1). Further, 52 differentially expressed lncRNAs (35 upregulated and 17 downregulated) were identified among 3849 lncRNA transcripts. The differentially expressed mRNAs were annotated as “biological process,” “cellular components” and “molecular functions” through gene ontology enrichment analysis. KEGG pathway enrichment analysis showed that cell cycle and renin-angiotensin pathways were upregulated in response to I/R, while protein digestion and absorption, hedgehog, neurotrophin, MAPK, and PI3K-Akt signaling were downregulated. The RNA-seq data was validated by qRT-PCR and western blot analyses of select mRNAs and lncRNAs. We observed that Bax, Caspase-3 and phospho-AKT were upregulated and Bcl-2 was downregulated in the spinal cord in response to renal injury. We also found negative correlations between three lncRNAs (TCONS_00042175, TCONS_00058568 and TCONS_00047728) and the degree of renal injury. These findings provide evidence for differential expression of lncRNAs and mRNAs in the lower thoracic spinal cord following I/R-induced AKI in rats and suggest potential clinical applicability.
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