MicroRNA expression profiling in acute kidney injury

Transl Res. 2022 Jun:244:1-31. doi: 10.1016/j.trsl.2021.11.010. Epub 2021 Dec 4.

Abstract

The aim of this study was to identify miRNAs that regulate AKI and develop their applications as diagnostic biomarkers and therapeutic agents. First, kidney tissues from two different AKI mouse models, namely, AKI induced by the administration of lipopolysaccharide (LPS) causing sepsis (LPS-AKI mice) and AKI induced by renal ischemia-reperfusion injury (IRI-AKI mice), were exhaustively screened for their changes of miRNA expression compared with that of control mice by microarray analysis followed by quantitative RT-PCR. The initial profiling newly identified miRNA-5100, whose expression levels significantly decreased in kidneys in both LPS-AKI mice and IRI-AKI mice. Next, the administration of miRNA-5100-mimic conjugated with a nonviral vector, polyethylenimine nanoparticles (PEI-NPs), via the tail vein significantly induced miRNA-5100 overexpression in the kidney and prevented the development of IRI-AKI mice by inhibiting several apoptosis pathways in vivo. Furthermore, serum levels of miRNA-5100 in patients with AKI were identified as significantly lower than those of healthy subjects. ROC analysis showed that the serum expression level of miRNA-5100 can identify AKI (cut-off value 0.14, AUC 0.96, sensitivity 1.00, specificity 0.833, p<0.05). These results suggest that miRNA-5100 regulates AKI and may be useful as a novel diagnostic biomarker and therapeutic target for AKI.

Keywords: ADA = Adriamycin; AKI = acute kidney injury; ANOVA = one-way analysis of variance; BCIP = 5-bromo-4-chloro-3-indolyl phosphate; BUN = blood urea nitrogen; CRE = creatinine; DAPI = 4′,6-diamidino-2-phenylindole-PBS; GAPDH = glyceraldehyde 3-phosphate dehydrogenase; H&E = hematoxylin and eosin; HIGA = high immunoglobulin A; IGFBP-7 = insulin like growth factor binding protein 7; IRI-AKI = ischemia-reperfusion injury-induced acute kidney injury; ISH = In situ hybridization; KIM-1 = kidney injury molecule 1; L-FABP = L-type fatty acid-binding protein; LPS-AKI = acute kidney injury induced by the intraperitoneal administration of lipopolysaccharide; LPS = lipopolysaccharide; NBT = nitroblue tetrazolium chloride; NGAL = neutrophil gelatinase-associated lipocalin; PEI-NPs = polyethylenimine nanoparticles; RNU6 = U6 Small Nuclear 1; TIMP-2 = tissue inhibitor of metalloproteinase 2; UUO = unilateral ureteral obstruction; eGFR = estimated glomerular filtration rate; mRNA = messenger ribonucleic acid; miRNAs = micro ribonucleic acid; qRT-PCR = quantitative real-time polymerase chain reaction.

MeSH terms

  • Acute Kidney Injury* / genetics
  • Animals
  • Biomarkers
  • Humans
  • Kidney / metabolism
  • Lipopolysaccharides
  • Mice
  • MicroRNAs* / genetics

Substances

  • Biomarkers
  • Lipopolysaccharides
  • MIRN5100 microRNA, human
  • MicroRNAs
  • Mirn5100 microRNA, mouse