MicroRNA expression profiling in acute kidney injury

• Published in: Translational research : the journal of laboratory and clinical medicine Vol. 244; pp. 1 - 31
• Main Authors: AOMATSU, AKINORI, KANEKO, SHOHEI, YANAI, KATSUNORI, ISHII, HIROKI, ITO, KIYONORI, HIRAI, KEIJI, OOKAWARA, SUSUMU, KOBAYASHI, YASUMA, SANUI, MASAMITSU, MORISHITA, YOSHIYUKI
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2022
• Subjects: Acute Kidney Injury - genetics; ADA = Adriamycin; AKI = acute kidney injury; Animals; ANOVA = one-way analysis of variance; BCIP = 5-bromo-4-chloro-3-indolyl phosphate; Biomarkers; BUN = blood urea nitrogen; CRE = creatinine; DAPI = 4′,6-diamidino-2-phenylindole-PBS; eGFR = estimated glomerular filtration rate; GAPDH = glyceraldehyde 3-phosphate dehydrogenase; H&E = hematoxylin and eosin; HIGA = high immunoglobulin A; Humans; IGFBP-7 = insulin like growth factor binding protein 7; IRI-AKI = ischemia-reperfusion injury-induced acute kidney injury; ISH = In situ hybridization; Kidney - metabolism; KIM-1 = kidney injury molecule 1; L-FABP = L-type fatty acid-binding protein; Lipopolysaccharides; LPS-AKI = acute kidney injury induced by the intraperitoneal administration of lipopolysaccharide; LPS = lipopolysaccharide; Mice; MicroRNAs - genetics; miRNAs = micro ribonucleic acid; mRNA = messenger ribonucleic acid; NBT = nitroblue tetrazolium chloride; NGAL = neutrophil gelatinase-associated lipocalin; PEI-NPs = polyethylenimine nanoparticles; qRT-PCR = quantitative real-time polymerase chain reaction; RNU6 = U6 Small Nuclear 1; TIMP-2 = tissue inhibitor of metalloproteinase 2; UUO = unilateral ureteral obstruction; IRI-AKI = ischemia-reperfusion injury-induced acute kidney injury; qRT-PCR = quantitative real-time polymerase chain reaction; LPS = lipopolysaccharide; mRNA = messenger ribonucleic acid; AKI = acute kidney injury; KIM-1 = kidney injury molecule 1; miRNAs = micro ribonucleic acid; NBT = nitroblue tetrazolium chloride; UUO = unilateral ureteral obstruction; HIGA = high immunoglobulin A; TIMP-2 = tissue inhibitor of metalloproteinase 2; CRE = creatinine; ISH = In situ hybridization; BCIP = 5-bromo-4-chloro-3-indolyl phosphate; eGFR = estimated glomerular filtration rate; BUN = blood urea nitrogen; ADA = Adriamycin; GAPDH = glyceraldehyde 3-phosphate dehydrogenase; NGAL = neutrophil gelatinase-associated lipocalin; RNU6 = U6 Small Nuclear 1; L-FABP = L-type fatty acid-binding protein; H&E = hematoxylin and eosin; PEI-NPs = polyethylenimine nanoparticles; DAPI = 4′,6-diamidino-2-phenylindole-PBS; ANOVA = one-way analysis of variance; LPS-AKI = acute kidney injury induced by the intraperitoneal administration of lipopolysaccharide; IGFBP-7 = insulin like growth factor binding protein 7
• ISSN: 1931-5244; 1878-1810; 1878-1810
• DOI: 10.1016/j.trsl.2021.11.010

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.