Concordant Changes of Plasma and Kidney MicroRNA in the Early Stages of Acute Kidney Injury: Time Course in a Mouse Model of Bilateral Renal Ischemia-Reperfusion

Abstract

BackgroundAcute kidney injury (AKI) is a syndrome characterized by the rapid loss of the kidney excretory function and is strongly associated with increased early and long-term patient morbidity and mortality. Early diagnosis of AKI is challenging; therefore we profiled plasma microRNA in an effort to identify potential diagnostic circulating markers of renal failure. The goal of the present study was to investigate the dynamic relationship of circulating and renal microRNA profiles within the first 24 hours after bilateral ischemia-reperfusion kidney injury in mice.Methodology/Principal FindingsBilateral renal ischemia was induced in C57Bl/6 mice (n = 10 per group) by clamping the renal pedicle for 27 min. Ischemia-reperfusion caused highly reproducible, progressive, concordant elevation of miR-714, miR-1188, miR-1897-3p, miR-877*, and miR-1224 in plasma and kidneys at 3, 6 and 24 hours after acute kidney injury compared to the sham-operated mice (n = 5). These dynamics correlated with histologic findings of kidney injury and with a conventional plasma marker of renal dysfunction (creatinine). Pathway analysis revealed close association between miR-1897-3p and Nucks1 gene expression, which putative downstream targets include genes linked to renal injury, inflammation and apoptosis.Conclusions/SignificanceSystematic profiling of renal and plasma microRNAs in the early stages of experimental AKI provides the first step in advancing circulating microRNAs to the level of promising novel biomarkers.

MicroRNA-1224 Splicing CircularRNA-Filip1l in an Ago2-Dependent Manner Regulates Chronic Inflammatory Pain via Targeting Ubr5

“…In our work, the abundant expression of miRNA-1224 was identified in the mouse spinal nucleus. Indeed, miRNA-1224 has been discovered to differentially express in the liver of fatty liver disease (Dolganiuc et al, 2009), and in different tissues of bladder cancer (Dudziec et al, 2011), inflammation, and acute injured kidney (Niu et al, 2011;Bellinger et al, 2014;Roy et al, 2017). miRNA-1224 can be also detected in hippocampus and the marginal division of the neostriatum in rats (Shu et al, 2013).…”

The potential use of biomarkers in predicting contrast-induced acute kidney injury

“…169 In an in vivo mouse model study, renal ischemia reperfusion caused the increase of several miRNA molecules in plasma and kidneys when compared with sham-treated mice, at 3 hours, 6 hours and 24 hours following the ischemic injury. 170 These molecules were correlated with plasma creatinine and histological observations of tubular degeneration and necrosis. In particular, the mRNA targets of one of these molecules, miR-1897-3p, included that of nuclear casein kinase and cyclin-dependent kinase substrate 1.…”

“…Targets of nuclear casein kinase and cyclindependent kinase substrate 1 have been implicated in renal injury, inflammation, and apoptosis. 170 Another study utilized serum samples from normal subjects and patients with AKI; miRNA molecules could be considered as markers of AKI. 171 Notably, several of the miRNA molecules had already been associated with kidney injury: in proximal tubule adhesion and trafficking during IRI (miR-127), in an in vivo mouse model of IRI and in patients with immunoglobulin A nephropathy (miR-146a), and in progression of chronic kidney disease (miR-29a).…”

Influence of remote ischemic conditioning and tramadol hydrochloride on oxidative stress in kidney ischemia/reperfusion injury in rats

“…Acute renal failure (ARF) is a high incidence syndrome, responsible for a high rate of morbidity and mortality, affecting about 30% to 50% of patients in intensive care units 1 . Among the characteristics of the ARF are decreased glomerular filtration rate, tubular necrosis, as well as abrupt increase in serum levels of urea and creatinine 48 hours 2 .…”