Urinary miR-16 transactivated by C/EBPβ reduces kidney function after ischemia/reperfusion-induced injury

Hsi Hsien Chen, Yi Fan Lan, Hsiao Fen Li, Ching Feng Cheng, Pei Fang Lai, Wei Hua Li, Heng Lin

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number27945
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Jun 14 2016

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CCAAT-Enhancer-Binding Protein-beta
Reperfusion Injury
Acute Kidney Injury
Kidney
MicroRNAs
Reperfusion
Ischemia
Lentivirus
In Situ Nick-End Labeling
B-Cell Lymphoma
Luciferases
Genetic Promoter Regions
Protein Binding
Creatinine
Epithelium
Biomarkers
Genome
Apoptosis

ASJC Scopus subject areas

  • General

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Urinary miR-16 transactivated by C/EBPβ reduces kidney function after ischemia/reperfusion-induced injury. / Chen, Hsi Hsien; Lan, Yi Fan; Li, Hsiao Fen; Cheng, Ching Feng; Lai, Pei Fang; Li, Wei Hua; Lin, Heng.

In: Scientific Reports, Vol. 6, 27945, 14.06.2016.

Research output: Contribution to journalArticle

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