Molecular Mechanisms of C/EBP-Β Regulates microRNA-16 and Its Clinical Application

Project: A - Government Institutionb - Ministry of Science and Technology

Description

Ischemia-reperfusion (I/R) injury of the kidney is a major cause of acute kidney injury (AKI). Both transcription factors and microRNAs (miRs) play major roles in I/R induced AKI. However, miRs controlled by transcription factors had not been characterized in AKI. Our previous data had identified the urinary microRNA-16 (miR-16) excretion was 100-fold higher in patients with AKI than without AKI or in normal controls (Fig.2), which indicating that the miR-16 may act as a biomarker of AKI. We further use the ingenuity systems pathway analysis to find that there are many transcription factors (such as C/EBP-β, PPAR/RXR and ATF3) binding site upstream on the promoter region of miR-16 (Fig.3), suggesting that the expression of miR-16 may be regulated by these transcription factors. Therefore, we propose that the transcription factor(s) may affect the pathophysiologic mechanisms in the kidneys after ischemia/reperfusion injury by regulate the miR-16 expression. In this proposal, we will evaluate following specific aims: 1. To identify which transcription factor(s) like C/EBP-β can regulate miR-16 transcriptional processing. 2. To clarify the pathophysiology mechanism of transcription factors like c/EBPβ can induce miR-16 expression in AKI by in vitro and in vivo models. 3. To search out other miRs except for miR-16 are also involved in transcription factor(s) like C/EBP-β regulation pathways. 4. To confirm the transcription factor(s) like C/EBP-β can act as therapeutic or diagnostic targets in AKI. This proposal will provide not only to clarify the relationship between transcription factor(s) and miRs in the renal pathophysiology but may also provide new therapeutic and diagnostic targets for AKI.
StatusFinished
Effective start/end date8/1/157/31/16

Keywords

  • acute kidney injury
  • microRNA
  • transcription factor