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A potential acute renal failure marker of MicroRNA494 modulates expression of the inducible transcription factor ATF3 and affects kidney function in a mice model of ischemia reperfusion
Author(s) -
Lan Yi-Fan,
Lai Pei Fang,
Lin Heng
Publication year - 2012
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.26.1_supplement.lb803
Subject(s) - cystatin c , acute kidney injury , atf3 , lipocalin , medicine , renal function , kidney , creatinine , renal ischemia , biomarker , urinary system , ischemia , reperfusion injury , gene expression , biology , gene , promoter , biochemistry
Background Previous reports have shown ATF3 plays a protective role in acute renal failure, ischemia/reperfusion (I/R) injury. The aim of this study was to analyze the potential regulation of ATF3 expression by microRNAs. Methods and Results In this study, we demonstrated that miR‐494 target 3′ untranslated region of ATF3 reporter and decreased ATF3 mRNA expression by reporter assay and molecular analysis. Overexpression lenti‐miR‐494 in mice kidney was significantly attenuate ATF3 mRNA and protein, accompany with I/R induced inflammatory related factor include IL‐6, MCP‐1, P‐selectin resulting cells apoptosis and renal function decreased. Importantly, the mice urinary miR‐494 was increased significantly earlier than serum creatinine after renal I/R. In clinical, the urinary miR‐494 expression was higher in acute kidney injury (AKI) patients than patients with no AKI and normal. Besides, we also find the increasing level of miR‐494 in urine of AKI is consistent with two of comparator AKI biomarker gelatinase‐associated lipocalin (NGAL) and cystatin C. Conclusion These data suggest that up‐regulation of miR‐494 contributes to inflammatory factor or adhesion molecule induced kidney injury after I/R via inhibition ATF3 expression and miR‐494 may act as an early specific and non‐invasive biomarker in AKI. The source of research supported from National Science Council (Taiwan).