CircNr1h4 regulates the pathological process of renal injury in salt‐sensitive hypertensive mice by targeting miR‐155‐5p

Abstract

Circular RNAs are a class of widespread and diverse endogenous RNAs that may regulate gene expression in various diseases, but their regulation and function in hypertensive renal injury remain unclear. In this study, we generated ribosomal-depleted RNA sequencing data from normal mouse kidneys and from injured mouse kidneys induced by deoxycorticosterone acetate-salt hypertension and identified at least 4900 circRNA candidates. A total of 124 of these circRNAs were differentially expressed between the normal and injured kidneys. Furthermore, we characterized one abundant circRNA, termed circNr1h4, which is derived from the Nr1h4 gene and significantly down-regulated in the injured kidneys. RNA sequencing data and qPCR analysis also showed many microRNAs and mRNAs, including miR-155-5p and fatty acid reductase 1 (Far1), were differentially expressed between the normal and injured kidney and related to circNr1h4. In vitro, the silencing of circNr1h4 or overexpression of miR-155-5p significantly decreased Far1 levels and increased reactive oxygen species. Mechanistic investigations indicated that circNr1h4 acts as a competing endogenous RNA for miR-155-5p, leading to regulation of its target gene Far1.Our study provides novel insight into the molecular mechanisms underlying kidney injury in hypertension, which will be required to develop therapeutic strategies of targeting circRNAs for hypertensive kidney injury. K E Y W O R D Scircular RNAs, hypertension, miRNAs, renal injury | 1701 LU et aL.

Acute Kidney Injury in Septic Patients Treated by Selected Nephrotoxic Antibiotic Agents—Pathophysiology and Biomarkers—A Review

“…The reaction between miR-155-5p and circNr1h4 is basically competitive, where the silencing of circNr1h4 or overexpression of miR-155-5p considerably decreased Far1 levels and increased ROS production. Therefore, miR-155-5p may be involved in the pathology of hypertensive kidney injury [ 73 ]. The involvement of miR-155-5p in the pathophysiological pathway to the development of diabetic kidney disease is probably explained by the signaling axis of p53 and sirt1 genes with regulation of autophagic and fibrotic processes in renal tubular injury.…”

Identification of Candidate Biomarkers for Salt Sensitivity of Blood Pressure by Integrated Bioinformatics Analysis

“…Although circular RNAs are attracting a good deal of attention, there has been little research in the field of circRNAs correlated with SSBP until now. Lu et al (2020) found that CircNr1h4 is involved in the pathological process of salt-sensitive hypertension with renal injury by sponging miR-155-5p as a ceRNA. Additionally, Cheng and Joe (2017) compared the circRNA expression of the Dahl salt-sensitive rat, the Dahl salt-resistant rat, the spontaneously hypertensive rat, and the Wistar Kyoto rat by microarray analysis.…”

Comprehensive analysis of circRNAs from steatotic livers after ischemia and reperfusion injury by next generation RNA sequencing

“…Numerous researchers have proved that circular RNAs can compete with mRNAs for target binding sites of miRNAs to in turn regulate the expression of mRNAs [15,23]. Furthermore, in recent years, the protein-binding function and the potentiality translating into short-peptide has attracted increasing attention [24,25], which may…”