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Transcription Factor C/EBP β‐Induced microRNA‐16 Inactivates BCL2 During Ischemia/Reperfusion and Reduce Kidney Function Heng Lin 1* , Hsi‐Hsien Cheng, 2 1 Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 2 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Author(s) -
Lin Heng,
Cheng HsiHsien
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.807.3
Subject(s) - apoptosis , kidney , renal ischemia , microrna , three prime untranslated region , ccaat enhancer binding proteins , untranslated region , transcription factor , ischemia , messenger rna , acute kidney injury , microbiology and biotechnology , medicine , chemistry , reperfusion injury , biology , endocrinology , gene , dna binding protein , biochemistry
Ischemia‐reperfusion (I/R) injury of the kidney is a major cause of AKI. Here, we report that miR‐16 was transactivated by CCAAT enhancer binding protein beta (C/EBP‐β) resulting in aggravated I/R induced kidney injury via inhibition of anti‐apoptotic protein, BCL‐2. Using TargetScan, we found that the 3' untranslated region (3'UTR) of proapoptotic protein, BCL‐2, is complementary to miR‐16 and miR‐16 decreased the fluorescent reporter activity by binding to the 3'UTR of BCL‐2. Furthermore, overexpression of miR‐16 in mice significantly attenuated renal function. As for the transcriptional regulation of miR‐16, upstream of promoter of miR‐16 containing C/EBP‐β binding site and overexpression of C/EBP‐β can induce miR‐16 after hypoxia/reoxygenation (H/R) condition in renal epithelium cells. Meanwhile, the level of miR‐16 was higher in mice infected with lentivirus containing C/EBP‐β compared with wild‐type mice after I/R and overexpression of antagonist of C/EBP‐βexpression in the kidney can reduce I/R induced kidney function injury and apoptosis. Taken together, our results provided new mechanistic insights for an understanding of the role of C/EBP‐β induced miR‐16 in AKI and revealed C/EBP‐β induced miR‐16 pathway as a potential target for therapeutic intervention.