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Updated: Mar 19, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Urinary miR-16 transactivated by C/EBPβ reduces kidney function after ischemia/reperfusion-induced injury
Hsi-Hsien Chen1,2, Yi-Fan Lan3, Hsiao-Fen Li3,4
1Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Abstract:
Ischemia-reperfusion (I/R) induced acute kidney injury (AKI) is regulated by transcriptional factors and microRNAs (miRs). However, modulation of miRs by transcriptional factors has not been characterized in AKI. Here, we found that urinary miR-16 was 100-fold higher in AKI patients. MiR-16 was detected earlier than creatinine in mouse after I/R. Using TargetScan, the 3'UTR of B-cell lymphoma 2 (BCL-2) was found complementary to miR-16 to decrease the fluorescent reporter activity. Overexpression of miR-16 in mice significantly attenuated renal function and increased TUNEL activity in epithelium tubule cells. The CCAAT enhancer binding protein beta (C/EBP-β) increased the expression of miR-16 after I/R injury. The ChIP and luciferase promoter assay indicated that about -1.0 kb to -0.5 kb upstream of miR-16 genome promoter region containing C/EBP-β binding motif transcriptionally regulated miR-16 expression. Meanwhile, the level of pri-miR-16 was higher in mice infected with lentivirus containing C/EBP-β compared with wild-type (WT) mice and overexpression of C/EBP-β in the kidney of WT mice reduced kidney function, increased kidney apoptosis, and elevated urinary miR-16 level. Our results indicated that miR-16 was transactivated by C/EBP-β resulting in aggravated I/R induced AKI and that urinary miR-16 may serve as a potential biomarker for AKI.
Insights
Urinary miR-16, elevated in acute kidney injury (AKI), is upregulated by CCAAT enhancer binding protein beta (C/EBP-β). This interaction exacerbates ischemia-reperfusion injury, suggesting miR-16 as a potential AKI biomarker.
Area of Science:
- Molecular Biology
- Renal Physiology
- Biochemistry
Background:
- Acute kidney injury (AKI) pathogenesis involves complex transcriptional and microRNA (miR) regulatory networks.
- The specific roles of transcriptional factors in modulating miRs during AKI remain largely uncharacterized.
- Identifying novel biomarkers for early AKI detection is crucial for timely intervention.
Purpose of the Study:
- To investigate the regulatory relationship between transcriptional factors and microRNAs in ischemia-reperfusion (I/R) induced AKI.
- To determine the functional role of miR-16 in AKI pathophysiology.
- To explore the potential of urinary miR-16 as a diagnostic biomarker for AKI.
Main Methods:
- Quantitative analysis of urinary miR-16 levels in AKI patients and mice.
- In vivo studies using mouse models of I/R injury to assess renal function, apoptosis, and miR-16 expression.
- Luciferase reporter assays, ChIP assays, and promoter analysis to elucidate the transcriptional regulation of miR-16 by C/EBP-β.
Main Results:
- Urinary miR-16 levels were significantly elevated in AKI patients and detected earlier than creatinine in mice post-I/R.
- Overexpression of miR-16 exacerbated renal dysfunction and tubular cell apoptosis in mice.
- CCAAT enhancer binding protein beta (C/EBP-β) was identified as a transcriptional activator of miR-16, with C/EBP-β binding motifs located in the miR-16 promoter region.
Conclusions:
- miR-16 is transactivated by C/EBP-β, contributing to the exacerbation of I/R-induced AKI.
- Urinary miR-16 demonstrates potential as an early diagnostic biomarker for AKI.
- Understanding the C/EBP-β/miR-16 axis provides insights into AKI pathogenesis and potential therapeutic targets.
