Early detection of cardiac surgery‑associated acute kidney injury by microRNA-21

Arvin, P; Samimagham, Hamid Reza; Montazerghaem, Hossein; Khayatian, Mahmood; Mahboobi, Hamidreza; Soufi, Farhad Ghadiri

doi:10.4149/bll_2017_120

Cited by 19 publications

(12 citation statements)

References 40 publications

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“…This is in keeping with other findings that urinary miR-21 appeared to be more associated with AKI prognosis than plasma miR-21 levels (39,40). Serum miR-21 levels were associated with the development of AKI when sampled before cardiac surgery (41) and 6 hours after cardiac surgery (42). In the latter study, urinary miR-21 levels were also associated with AKI (42).…”

Section: Microrna As Biomarkers Of Kidney Diseasesupporting

confidence: 90%

“…Serum miR-21 levels were associated with the development of AKI when sampled before cardiac surgery (41) and 6 hours after cardiac surgery (42). In the latter study, urinary miR-21 levels were also associated with AKI (42). Interestingly, ischemic preconditioning could increase endogenous miR-21 expression and further protect kidney function (43).…”

Section: Microrna As Biomarkers Of Kidney Diseasementioning

confidence: 87%

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MicroRNAs in AKI and Kidney Transplantation

Ledeganck

Gielis

Abramowicz

et al. 2019

CJASN

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MicroRNAs are epigenetic regulators of gene expression at the posttranscriptional level. They are involved in intercellular communication and crosstalk between different organs. As key regulators of homeostasis, their dysregulation underlies several morbidities including kidney disease. Moreover, their remarkable stability in plasma and urine makes them attractive biomarkers. Beyond biomarker studies, clinical microRNA research in nephrology in recent decades has focused on the discovery of specific microRNA signatures and the identification of novel targets for therapy and/or disease prevention. However, much of this research has produced equivocal results and there is a need for standardization and confirmation in prospective trials. This review aims to provide an overview of general concepts and available clinical evidence in both the pathophysiology and biomarker fields for the role of microRNA in AKI and kidney transplantation. LDL Ago HDL MV Mature miRNA miRISC miRNA duplex Pre-miRNA Transcription MV MV MV E AB Interstitium Active release Passive release Capillary Ago Dicer XPO-5 Pri-miRNA Mirtron RNA pol II Drosha-DGCR8 Figure 1. | MicroRNA biogenesis and function.microRNA coding regions in the human genome are found either intergenic or in the introns of annotated genes. microRNA synthesis starts in the nucleus where most of the miRs are transcribed by RNA polymerase II into primary miR transcripts (pri-miR) of several kilobases that contain local stem-loop structures. The first step of miR maturation is cleavage at the stem of the hairpin structure by a microprocessor complex consisting of Drosha (an RNase III protein) together with its cofactor DiGeorge Syndrome Critical Region 8 (DGCR8), which releases a small hairpin structure of 70 nucleotides that is termed a precursor miR (pre-miR). After nuclear processing, pre-miRs are exported to the cytoplasm by exportin 5 (XPO-5), where they are cleaved near the terminal loop by another RNase enzyme called Dicer, thereby releasing an approximately 22 nucleotide miR duplex. This duplex is loaded onto an AGO protein to generate the microRNA-induced silencing complex (miRISC). One strand (guide strand) remains in the AGO protein as a biologically active miR whereas the other stand (passenger strand, known as miR*) is degraded. The mature miR as part of the effector RISC binds to the 39UTR region of the mRNA and mediates mRNA degradation, destabilization, or translational inhibition. Apart from this canonical pathway, there is an alternative "mirtron" pathway, independent from Drosha and DGCR8. Mirtrons are miRs that originate from spliced-out introns and are created when small RNAs bind to the termini of small intronic hairpins. Pre-microRNA hairpins with 39 overhangs are so formed and can mature into 22 nucleotides structures, which look and function as normal miRs. microRNAs exert their repressive function intracellularly, but are also released into the extracellular compartment, with this initiating theirroleasimportantintercellular communicators as theyare ta...

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Section: Microrna As Biomarkers Of Kidney Diseasesupporting

confidence: 90%

Section: Microrna As Biomarkers Of Kidney Diseasementioning

confidence: 87%

MicroRNAs in AKI and Kidney Transplantation

Ledeganck

Gielis

Abramowicz

et al. 2019

CJASN

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“…MiR-21 was up-regulated in several distinct animal models of kidney diseases as well as both human AKI and chronic kidney disease (CKD) (Loboda et al, 2016 ). Thus, miR-21 is considered a potential biomarker for cardiac surgery-associated acute kidney injury, hypertensive kidney injury and fibrosis (Gaede et al, 2016 ; Arvin et al, 2017 ; Chen et al, 2017 ). However, the effect of miR-21 on renal injury remains controversial.…”

Section: Discussionmentioning

confidence: 99%

miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation

et al. 2018

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Renal tubular injury and innate immune responses induced by hypoxia contribute to acute kidney injury. Accumulating evidence suggests that miR-21 overexpression protects against kidney ischemia injury. Additionally, miR-21 emerges as a key inhibitor in dendritic cell maturation. Thus, we hypothesized that miR-21 protects the kidney from IR injury by suppressing epithelial cell damage and inflammatory reaction. In this study, we investigated effects of miR-21 and its signaling pathways (PTEN/AKT/mTOR/HIF, PDCD4/NFκ-B) on kidney ischemia/reperfusion (IR) injury in vitro and in vivo. The results revealed that IR increased miR-21, HIF1α, and 2α expression in vivo and in vitro. MiR-21 interacted with HIF1α and 2α through the PTEN/AKT/mTOR pathway. Moreover, inhibition of miR-21 activated PDCD4/NFκ-B pathways, which are critical for dendritic cell maturation. Renal IR triggers local inflammation by inducing the dendritic cell maturation and promoting the secretion of IL-12, IL-6, and TNF-α cytokines. Knockdown of miR-21 intensified the effect of IR on tubular epithelial cell apoptosis and dendritic cell maturation. Our results suggested that IR-inducible miR-21 protects epithelial cells from IR injury via a feedback interaction with HIF (PTEN/AKT/mTOR/HIF/miR-21) and by inhibiting maturation of DCs through the PDCD4/NF-κB pathway. These findings highlight new therapeutic opportunities in AKI.

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“…One clinical study found that miR-21 levels increased both in plasma and urine with increasing AKI severity after adult cardiac surgery [ 63 ]. However, another clinical study found decreased, but not increased, expression of miR-21 in cardiac surgery-associated AKI patients [ 64 ]. Recently, a large-scale study found that urine and blood miR-21 expression in the remote ischemic preconditioning group increased significantly in children with congenital heart disease undergoing cardiopulmonary bypass surgery [ 65 ].…”

Section: Mirnas In Acute Kidney Injurymentioning

confidence: 99%

MicroRNAs as Biomarkers and Therapeutic Targets in Inflammation- and Ischemia-Reperfusion-Related Acute Renal Injury

Chen

et al. 2020

IJMS

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Acute kidney injury (AKI), caused mainly by ischemia-reperfusion, sepsis, or nephrotoxins (such as contrast medium), is identified by an abrupt decline in kidney function and is associated with high morbidity and mortality. Despite decades of efforts, the pathogenesis of AKI remains poorly understood, and effective therapies are lacking. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level to control cell differentiation, development, and homeostasis. Additionally, extracellular miRNAs might mediate cell–cell communication during various physiological and pathological processes. Recently, mounting evidence indicates that miRNAs play a role in the pathogenesis of AKI. Moreover, emerging research suggests that because of their remarkable stability in body fluids, microRNAs can potentially serve as novel diagnostic biomarkers of AKI. Of note, our previous finding that miR-494 is rapidly elevated in urine but not in serum provides insight into the ultimate role of urine miRNAs in AKI. Additionally, exosomal miRNAs derived from stem cells, known as the stem cell secretome, might be a potential innovative therapeutic strategy for AKI. This review aims to provide new data obtained in this field of research. It is hoped that new studies on this topic will not only generate new insights into the pathophysiology of urine miRNAs in AKI but also might lead to the precise management of this fatal disease.

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Early detection of cardiac surgery‑associated acute kidney injury by microRNA-21

Cited by 19 publications

References 40 publications

MicroRNAs in AKI and Kidney Transplantation

MicroRNAs in AKI and Kidney Transplantation

miR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation

MicroRNAs as Biomarkers and Therapeutic Targets in Inflammation- and Ischemia-Reperfusion-Related Acute Renal Injury

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