MicroRNA-494 reduces ATF3 expression and promotes AKI

Yi Fan Lan, Hsi Hsien Chen, Pei Fang Lai, Ching Feng Cheng, Yen Ta Huang, Yi Chao Lee, Tzen-Wen Chen, Heng Lin

Research output: Contribution to journalArticle

64 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2012-2023
Number of pages12
JournalJournal of the American Society of Nephrology
Volume23
Issue number12
DOIs
Publication statusPublished - 2012

Fingerprint

Activating Transcription Factor 3
MicroRNAs
Kidney
Reperfusion
Ischemia
Apoptosis
P-Selectin
Chemokine CCL2
Reperfusion Injury
Interleukin-6
Creatinine
Necrosis
Up-Regulation
Biomarkers
Serum

ASJC Scopus subject areas

  • Nephrology

Cite this

MicroRNA-494 reduces ATF3 expression and promotes AKI. / Lan, Yi Fan; Chen, Hsi Hsien; Lai, Pei Fang; Cheng, Ching Feng; Huang, Yen Ta; Lee, Yi Chao; Chen, Tzen-Wen; Lin, Heng.

In: Journal of the American Society of Nephrology, Vol. 23, No. 12, 2012, p. 2012-2023.

Research output: Contribution to journalArticle

Lan, Yi Fan ; Chen, Hsi Hsien ; Lai, Pei Fang ; Cheng, Ching Feng ; Huang, Yen Ta ; Lee, Yi Chao ; Chen, Tzen-Wen ; Lin, Heng. / MicroRNA-494 reduces ATF3 expression and promotes AKI. In: Journal of the American Society of Nephrology. 2012 ; Vol. 23, No. 12. pp. 2012-2023.
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