Abstract
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.
Highlights
Acute kidney injury (AKI) is a major renal disease with increasing incidence and mortality [1]
The functional analysis and histopathological validation was performed to ensure that all I/R-induced acute kidney injury (AKI) rats used for sequencing experiments showed significant acute renal failure
We observed that 45 min of ischemia resulted in increased serum creatinine (302.5 ± 49.8μM in I/R; 27.2 ± 1.6μM in sham; P
Summary
Acute kidney injury (AKI) is a major renal disease with increasing incidence and mortality [1]. Activation of renal sympathetic nervous system has been implicated in ischemic AKI [14, 15]. Our previous study showed that the T9 spinal cord segment was primarily involved in sympathetic regulation of renal function [17]. The excitability of renal sympathetic nervous system increased during I/R-induced acute renal failure [18, 19]. Blocking of renal sympathetic nervous activation or denervated kidneys before renal ischemia ameliorated post-ischemic renal injury to some extent [20,21,22]. We postulated that spinal cord played an important role in acute kidney injury
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