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Review
. 2024 Feb 8:15:1230742.
doi: 10.3389/fimmu.2024.1230742. eCollection 2024.

The role of non-protein-coding RNAs in ischemic acute kidney injury

Fatemeh Sabet Sarvestani #  1 , Afsoon Afshari #  2 , Negar Azarpira  1
Affiliations
Review

The role of non-protein-coding RNAs in ischemic acute kidney injury

Fatemeh Sabet Sarvestani et al. Front Immunol. .

Abstract

Acute kidney injury (AKI) is a condition characterized by a rapid decline in kidney function within a span of 48 hours. It is influenced by various factors including inflammation, oxidative stress, excessive calcium levels within cells, activation of the renin-angiotensin system, and dysfunction in microcirculation. Ischemia-reperfusion injury (IRI) is recognized as a major cause of AKI; however, the precise mechanisms behind this process are not yet fully understood and effective treatments are still needed. To enhance the accuracy of diagnosing AKI during its early stages, the utilization of innovative markers is crucial. Numerous studies suggest that certain noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), play a central role in regulating gene expression and protein synthesis. These ncRNAs are closely associated with the development and recovery of AKI and have been detected in both kidney tissue and bodily fluids. Furthermore, specific ncRNAs may serve as diagnostic markers and potential targets for therapeutic interventions in AKI. This review aims to summarize the functional roles and changes observed in noncoding RNAs during ischemic AKI, as well as explore their therapeutic potential.

Keywords: acute kidney injury; circular RNAs; ischemia; lncRNAs; miRNAs; noncoding RNAs.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The KDIGO guidelines for AKI in 2012.
Figure 2
Figure 2
Molecular processes that happen during ischemic AKI.
Figure 3
Figure 3
The diagram showing different members of human RNA transcriptome; RNA molecules are divided into various categories according their size, localization, and functionality. circRNA, circular RNA; lncRNA, long noncoding RNA; miRNA, microRNA; piRNA, piwi-interacting RNA; rasiRNA, repeat-associated small interfering RNA; scaRNA, small cajal body-specific RNA; siRNA, small interfering RNA; snoRNA, small nucleolar RNA; snRNA, small nuclear RNA; tiRNA, transfer RNA–derived stress-induced small RNA; tRNA, transfer RNA.
Figure 4
Figure 4
The process of producing intergenic and intronic lncRNAs; (A) the lncRNAs produced from the non-coding regions between protein-coding genes are termed intergenic lncRNAs, (B) the lncRNAs produced from the protein-coding genes are termed intronic lncRNAs that might be produced from different parts of the gene.
Figure 5
Figure 5
The process of producing sense (exonic) and antisense lncRNAs; (A) lncRNAs originating from the exons of the protein coding segment of genes produce exonic lncRNAs, (B) Antisense lncRNAs or NATs, are produced in the opposite direction to protein-coding genes.
Figure 6
Figure 6
The process of producing bidirectional and miscellaneous lncRNAs; (A) bidirectional lncRNAs start transcription within 1000 base pairs to the start sites of the genes and proceed in the opposite direction, (B) Several other types of lncRNAs such as pseudo-lncRNAs (resulting from pseudogenes), T-UCR lncRNAs (derived from ultra-conserved regions), enhancer lncRNAs (transcribed from enhancer regions), and promoter lncRNAs (transcribed from promoter sequences), are categorized as miscellaneous lncRNAs.
Figure 7
Figure 7
The circRNA production processes; this process might be done by different methods and by using different molecules; beside the canonical process (A) there is also other methods that is known as direct back splicing and lariat-driven circularization (B) that several other molecules are functioning together to make these processes happen.
Figure 8
Figure 8
circRNAs functionality is executed thru different mechanisms, circRNAs act as (A) transcription regulators and transcription factors and cell cycle checkpoints are found to be targets of circRNA regulation, (B) miRNA sponges; as are rich in miRNA-binding sites sponges miRNAs and control their inhibitory effects, (C) protein decoys; circRNAs containing RBP binding sequences decoys for these proteins, (D) protein scaffolds; regulate intracellular protein/protein and protein/RNA interactions.
Figure 9
Figure 9
The probable pathway for controlling ischemic AKI.
See this image and copyright information in PMC

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The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by Transplant Research Center, Shiraz University of Medical Sciences.

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