Expression, Circulation, and Excretion Profile of MicroRNA-21,-155, and-18a Following Acute Kidney Injury

被引:170
作者
Saikumar, Janani
Hoffmann, Dana
Kim, Tae-Min [2 ]
Ramirez Gonzalez, Victoria [3 ]
Zhang, Qin [4 ]
Goering, Peter L. [4 ]
Brown, Ronald P. [4 ]
Bijol, Vanesa [5 ]
Park, Peter J. [2 ]
Waikar, Sushrut S.
Vaidya, Vishal S. [1 ,6 ]
机构
[1] Harvard Univ, Sch Med, Dept Med,Renal Div, Brigham & Womens Hosp,Lab Kidney Toxicol & Regene, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA
[3] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nefrol & Metab Mineral, Mexico City, DF, Mexico
[4] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA
[5] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[6] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA
关键词
MicroRNAs; kidney; biomarker; ischemia/reperfusion injury; nephrotoxicity; ACUTE-RENAL-FAILURE; DOWN-REGULATION; CELL CARCINOMA; MICRORNAS; BIOMARKERS; CANCER; IDENTIFICATION; DISEASE; SERUM; RISK;
D O I
10.1093/toxsci/kfs210
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
MicroRNAs (miRNAs) are endogenous noncoding RNA molecules that are involved in post-transcriptional gene silencing. Using global miRNA expression profiling, we found miR-21, -155, and 18a to be highly upregulated in rat kidneys following tubular injury induced by ischemia/reperfusion (I/R) or gentamicin administration. Mir-21 and -155 also showed decreased expression patterns in blood and urinary supernatants in both models of kidney injury. Furthermore, urinary levels of miR-21 increased 1.2-fold in patients with clinical diagnosis of acute kidney injury (AKI) (n = 22) as compared with healthy volunteers (n = 25) (p < 0.05), and miR-155 decreased 1.5-fold in patients with AKI (p < 0.01). We identified 29 messenger RNA core targets of these 3 miRNAs using the context likelihood of relatedness algorithm and found these predicted gene targets to be highly enriched for genes associated with apoptosis or cell proliferation. Taken together, these results suggest that miRNA-21 and -155 could potentially serve as translational biomarkers for detection of AM and may play a critical role in the pathogenesis of kidney injury and tissue repair process.
引用
收藏
页码:256 / 267
页数:12
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