Identification of crucial miRNAs and the targets in renal cortex of hypertensive patients by expression profiles

Abstract

Backgrounds: Defect in kidney is one major reason of hypertension. The study aimed ao uncovering the regulatory mechanisms of miRNAs and the targets in hypertensive kidney.Methods: Gene expression profile of GSE28345 and miRNA expression profile of GSE28283 were downloaded from GEO database. After data preprocessing, differently expressed genes (DEGs) and miRNAs (DE-miRs) were identified using limma package. Then targets of miRNAs were predicted according to information in relevant databases. Function and pathway enrichment analyses were performed for DEGs using DAVID software. Furthermore, protein–protein interaction (PPI) networks were constructed for up- and down-regulated genes, respectively, using the Cytoscape. Additionally, for down-regulated DEGs, the integrated regulatory network was established combining PPI network with the miRNA–mRNA interactions.Results: As a result, 285 DEGs were identified, including 177 up-regulated and 108 down-regulated genes. Combined with the predicted targets of miRNAs, 22 up-regulated DE-miRs were identified. In the integrated network for down-regulated DEGs, three crucial nodes were identified as ASPN, COL12A1, and SCN2A. ASPN was predicted as target of miR-21 and miR-374b, and COL12A1 was the target of miR-30e, miR-21, and miR-195, while SCN2A was the target of miR-30e, miR-374b, and miR-195. Notably, COL12A1 and ASPN were linked with each other in the network.Conclusion: Three crucial genes were identified in hypertensive kidney, such as COL12A1, ASPN, and SCN2A. ASPN might co-function with COL12A1, and they both might be the targets of miR-21. SCN2A might be a novel target of miR-30e and miR-374b. However, more experiments are needed to validate these results.

Genetic Contributors of Incident Stroke in 10,700 African Americans With Hypertension: A Meta-Analysis From the Genetics of Hypertension Associated Treatments and Reasons for Geographic and Racial Differences in Stroke Studies

“…Additional significant findings include those variants located in COL12A1. This gene encodes the collagen alpha chain of type XII collagen, which interacts with type 1 collagen-containing fibrils (UniProt, 2021), and is a predicted target of the human microRNA-21, which is induced by Angiotensin II (Wang et al, 2017). Angiotensin II is the principal effector hormone of the renin-angiotensin system and increases blood pressure through vasoconstriction and increased sodium and water retention (de Leeuw, 1999), which is clinically relevant to our hypertensive study base.…”

Tribulus terrestris L. protects glomerular endothelial cells via the miR155-H2AC6 interaction network in hypertensive renal injury

“…Numerous studies have shown that miRNAs are biomarkers and therapeutic targets (37)(38)(39)(40). Thus, we constructed a miRNA-mRNA interaction network to uncover the underlying molecular mechanism in hypertensive renal injury.…”

MiRNAs as potential biomarker of kidney diseases: A review

“…Apart from this miRNA, miR‐214‐3p and miR‐29 are also involved in the development of HT 82,85 . Guohua et al, determined ASPN, COL12A1, and SCN2A as downregulated genes in hypertensive patients which predicted as targets of miRNA‐374b, miRNA‐21, miRNA‐30e and miRNA‐195 86 …”