title: MicroRNA-494 reduces ATF3 expression and promotes AKI.
abstract: MicroRNA-494 mediates apoptosis and necrosis in several types of cells, but its renal target and potential role in AKI are unknown. Here, we found that microRNA-494 binds to the 3'UTR of activating transcription factor 3 (ATF3) and decreases its transcription. In mice, overexpression of microRNA-494 significantly attenuated the level of ATF3 and induced inflammatory mediators, such as IL-6, monocyte chemotactic protein-1, and P-selectin, after renal ischemia/reperfusion, exacerbating apoptosis and further decreasing renal function. Activation of NF-κB mediated this proinflammatory response. In this ischemia/reperfusion model, urinary levels of microRNA-494 increased significantly before the rise in serum creatinine. In humans, urinary microRNA-494 levels were 60-fold higher in patients with AKI than normal controls. In conclusion, upregulation of microRNA-494 contributes to inflammatory or adhesion molecule-induced kidney injury after ischemia/reperfusion by inhibiting expression of ATF3. Furthermore, microRNA-494 may be a specific and noninvasive biomarker for AKI.
authors.affiliation: PhD Program in Pharmacology and Toxicology, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Lan
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Chen
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Lai
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Huang
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Lee
authors.forename: Tzen-Wen
authors.initials: TW
authors.lastname: Chen
authors.forename: Heng
authors.initials: H
authors.lastname: Lin
mesh_terms: D020413:3' Untranslated Regions; D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D058186:Acute Kidney Injury / Q000378:metabolism*; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016180:Lentivirus Infections; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism* / Q000652:urine*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D051700:Activating Transcription Factor 3; D000209:Acute-Phase Proteins; C103002:Atf3 protein, mouse; D015415:Biomarkers; D015850:Interleukin-6; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; C547168:MIRN494 microRNA, human; D035683:MicroRNAs; C550178:Mirn494 microRNA, mouse; D011518:Proto-Oncogene Proteins; D003404:Creatinine