Differential gene and lncRNA expression in the lower thoracic spinal cord following ischemia/reperfusion-induced acute kidney injury in rats
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Qing-Quan Liu1,*, Hui Liu1,*, Zhi-Gang He2, Shi-Jie Zhang1, Bao-Wen Liu2, Le Wang1, Wen-Hui Qiu1, Qing Xu1, Hong-Bing Xiang2 and Yong-Man Lv1
1Department of Nephrology, Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, PR China
2Department of Anesthesiology and Pain Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, PR China
*These authors have contributed equally to this work and should be considered co-first authors
Hong-Bing Xiang, email: email@example.com
Yong-Man Lv, email: firstname.lastname@example.org
Keywords: renal ischemia/reperfusion, lncRNA, spinal cord, high-throughput sequencing, transcriptomes
Received: July 10, 2016 Accepted: May 21, 2017 Published: June 20, 2017
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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