Identification of biomarkers and pathways in hypertensive nephropathy based on the ceRNA regulatory network

Zhen Wang,Yingxia Yang,Zhongjie Liu,Lei Kang

doi:10.1186/s12882-020-02142-8

Abstract

BackgroundHypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension, which seriously affect people’s life. The purpose of this study was to identify the potential biomarkers of HTN and understand its possible mechanisms.MethodsThe dataset numbered GSE28260 related to hypertensive and normotensive was downloaded from NCBI Gene Expression Omnibus. Then, the differentially expressed RNAs (DERs) were screened using R limma package, and functional analyses of DE-mRNA were performed by DAVID. Afterwards, a ceRNA network was established and KEGG pathway was analyzed based on the Gene Set Enrichment Analysis (GSEA) database. Finally, a ceRNA regulatory network directly associated with HTN was proposed.ResultsA total of 947 DERs were identified, including 900 DE-mRNAs, 20 DE-lncRNAs and 27 DE-miRNAs. Based on these DE-mRNAs, they were involved in biological processes such as fatty acid beta-oxidation, IRE1-mediated unfolded protein response, and transmembrane transport, and many KEGG pathways like glycine, serine and threonine metabolism, carbon metabolism. Subsequently, lncRNAs KCTD21-AS1, LINC00470 and SNHG14 were found to be hub nodes in the ceRNA regulatory network. KEGG analysis showed that insulin signaling pathway, glycine, serine and threonine metabolism, pathways in cancer, lysosome, and apoptosis was associated with hypertensive. Finally, insulin signaling pathway was screened to directly associate with HTN and was regulated by mRNAs PPP1R3C, PPKAR2B and AKT3, miRNA has-miR-107, and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG.ConclusionsInsulin signaling pathway was directly associated with HTN, and miRNA has-miR-107 and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG were the biomarkers of HTN. These results would improve our understanding of the occurrence and development of HTN.

Highlights

Hypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension, which seriously affect people’s life
These results would improve our understanding of the occurrence and development of HTN
The Differentially expressed RNA (DER) between hypertensive and normotensive were screened using limma package, and 947 DERs were filtered based on the thresholds of False discovery rate (FDR) < 0.05 and |log2FC| > 1 (Fig. 1a)

Summary

Introduction

Hypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension, which seriously affect people’s life. The purpose of this study was to identify the potential biomarkers of HTN and understand its possible mechanisms. The kidney is an important organ causing hypertension, and the target organ of hypertensive damage [1]. Hypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension [2]. When hypertension lasts for 5–10 years, renal arteriolosclerosis, thickening of tube walls, and narrowing of bureaucratic cavities can occur, which will trigger substantial ischemic injury to the kidney [3]. Due to the increasing occurrence and mortality rate of HTN, molecular mechanisms of hypertensive effect on kidney are urgent to be revealed, which is helpful for the early diagnosis and targeted control therapy of HTN

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Conclusion