Increased Serum and Urinary MicroRNAs in Children with Idiopathic Nephrotic Syndrome

Abstract

BACKGROUND MicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS). METHODS We obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases. Serum miRNAs were analyzed with the TaqMan Low Density Array and then validated with a quantitative reverse-transcription PCR assay with 126 individual samples. Moreover, we collected paired serum samples from 50 patients before and after treatment to determine the value of these miRNAs for condition assessment. In addition, urine samples from these patients were examined for candidate miRNAs. RESULTS The concentrations of serum miR-30a-5p, miR-151-3p, miR-150, miR-191, and miR-19b were highly increased in NS children compared with controls (P < 0.0001). The urinary miR-30a-5p concentration was also increased in NS (P = 0.001). The area under the ROC curve and the odds ratio for the combined 5 serum miRNAs were 0.90 (95% CI, 0.86–0.94; P < 0.0001) and 40.7 (95% CI, 6.06–103; P < 0.0001), respectively. Moreover, the concentrations of the 5 serum miRNAs and urinary miR-30a-5p markedly declined with the clinical improvement of the patients. CONCLUSIONS We determined that 5 distinct serum miRNAs and urinary miR-30a-5p were increased in NS children. These circulating or urinary miRNAs may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS.

Overview of the cellular and molecular basis of kidney fibrosis

“…For e.g., in experimental models of kidney fibrosis, the number of interstitial myofibroblasts was significant reduced by a demethylating agent, a histone deacetylase inhibitor, and anti-microRNA-21 therapy, noting that microRNA-21 unregulation has been reported in several animal and human CKD tissue samples. 34, 35, 36, 37 Epigenetic regulation of fibrotic responses provides a new way to investigate environmental influences on genetically regulated pathways, such as kidney fibrosis.…”

MiR‐30a attenuates immunosuppressive functions of IL‐1β‐elicited mesenchymal stem cells via targeting TAB3

“…To date, miRNAs are regarded as having critical roles in distinct biological processes, including development, differentiation and oncogenesis [17,18]. Thus the expression patterns of miRNAs may reflect the changes of pathophysiological states or progression of particular diseases [19]. Indeed, large differences in the expression profiles of miRNAs were reported in placental tissue or tissue- Abbreviations: miRNAs, microRNAs; CCNE2, cyclin E2; COX2, cyclooxygenase 2; IL, interleukin; MSCs, mesenchymal stem cells; PE, preeclampsia; TAB3, transforming growth factor-b-activated kinase 1 binding protein 3; NF-jB, nuclear factor jB;…”

Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by MicroRNA

“…23,24 Furthermore, children with nephrotic syndrome revealed an increased serum level of miR-19b. 25 One might speculate whether such a change is linked with the diminished 11β-HSD2 activity reported by our group in patients with the nephrotic syndrome. 26 It is shown that miR190a upregulated by mechanical stress in podocytes 28 might be linked with the shear stress-mediated downregulation of 11β-HSD2.…”

“…Proangiogenic, nephritic syndrome [24][25][26] rno-miR-29b-3p 1.2×10 -3 Fibrotic pathway, collagen genes, Mmp2, Itgb1 of a specific mRNA. As clearly indicated in Table S1, different programs predict different members of the miRNA family to bind to the 3′-UTR of the HSD11B2 mRNA, an observation known for other genes.…”