Gene expression changes induced by over-expression of miR-181b-5p in db/db mouse. Gene expression changes induced by over-expression of miR-181b-5p in db/db mouse

The microRNAs (miRNAs) that can influence 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, kidneys from two DKD mouse models were screened for differences in miRNA expression from control mice. We found that miRNA-125b-5p and miRNA-181-5p were specifically differentially expressed in the kidneys of DKD mice. Next, we administered miRNA-181b-5p-mimic to DKD mice, which reduced the albuminuria and abnormal mesangial expansion. Pathway analysis revealed that overexpression of miRNA-181-5p significantly altered the expression of 51 genes in the kidneys of DKD mice. Furthermore, the serum level of miRNA-125b-5p was significantly higher and that of miRNA-181-5p was lower in patients with DKD than in patients with other kidney diseases. 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. Overall design: Gene microarray analysis was performed on kidney tissue from each group: normal mice (n=2), untreated db/db mice (n=2), db/db mice administered miRNA-181b-5p-mimic-PEI-NPs (n=2), and db/db mice administered control-miRNA-PEI-NPs (n=2).