MicroRNA Expression Profiling in Diabetic Kidney Disease

• Published in: Translational Research Vol. 237; pp. 31 - 52
• Main Authors: Ishii, Hiroki, Kaneko, Shohei, Yanai, Katsunori, Aomatsu, Akinori, Hirai, Keiji, Ookawara, Susumu, Morishita, Yoshiyuki
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2021; Elsevier BV
• Subjects: 4′,6-diamidino-2-phenylindole; Aged; Animals; Biomarkers; BMI; body mass index; control for the senescence-accelerated mouse; DAPI; Diabetes Mellitus; diabetic kidney disease; Diabetic Nephropathies; DKD; eGFR; estimated glomerular filtration rate; Female; FITC; fluorescein isothiocyanate; HDL high-density lipoprotein; HIGA; high immunoglobulin A; Humans; IRI; ischemia-reperfusion injury; Kidney; LDL; low-density lipoprotein; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Middle Aged; not significant; PEI-NPs; polyethylenimine nanoparticles; RNU6; SAMP; SAMR; senescence-accelerated mouse; Transcriptome; U6 Small Nuclear 1; UACR; unilateral ureteral obstruction; urine albumin-to-creatinine ratio; UUO; eGFR; IRI; ns; DAPI; UUO; FITC; PEI-NPs; LDL; SAMR; HDL high-density lipoprotein; SAMP; HIGA; RNU6; DKD; UACR; BMI
• ISSN: 1931-5244; 1878-1810; 1878-1810
• DOI: 10.1016/j.trsl.2021.05.008

The microRNAs (miRNAs) that can regulate diabetic kidney disease (DKD) have not been fully characterized. The aim of this study was to identify the miRNAs that affect DKD and could be used as specific biomarkers or therapeutic agents. First, kidney tissues from two DKD mouse models and control mice were screened for differences in miRNA expression by microarray analysis followed by quantitative real-time reverse transcription-PCR. Six miRNAs were differentially expressed from controls in both DKD mouse models. Among them, miRNA-125b-5p and miRNA-181b-5p were exclusively downregulated in the DKD mouse model. Next, we administered miRNA-181b-5p-mimic to DKD mice, which reduced the albuminuria and abnormal mesangial expansion. Pathway analysis and database research revealed that overexpression of miRNA-181b-5p significantly altered the expression of seven mRNAs in six known signaling pathways in the kidneys of DKD mice. Furthermore, the serum level of miRNA-125b-5p was significantly higher in patients with DKD (1.89±0.40-fold, P<0.05) compared with patients with other kidney diseases (0.94±0.13-fold) and healthy subjects (1.00±0.19-fold). Serum levels of miRNA-181b-5p were lower in patients with DKD (0.30±0.06-fold, P<0.05) compared with patients with other kidney diseases (1.06±0.20-fold) and healthy subjects (1.00±0.16-fold). These results suggest that miRNA-125b-5p and miRNA-181b-5p may represent novel diagnostic biomarkers and that miRNA-181b-5p may represent a therapeutic target for DKD.