Expression, circulation, and excretion profile of microRNA-21, -155, and -18a following acute kidney injury.
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 AKI and may play a critical role in the pathogenesis of kidney injury and tissue repair process.
Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Janani
J
Saikumar
Dana
D
Hoffmann
Tae-Min
TM
Kim
Victoria Ramirez
VR
Gonzalez
Qin
Q
Zhang
Peter L
PL
Goering
Ronald P
RP
Brown
Vanesa
V
Bijol
Peter J
PJ
Park
Sushrut S
SS
Waikar
Vishal S
VS
Vaidya
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics / Q000652:urine*; D000465:Algorithms; D000818:Animals; D016022:Case-Control Studies; D005839:Gentamicins / Q000633:toxicity; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics* / Q000652:urine; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
D005839:Gentamicins; C524942:MIRN155 microRNA, human; C522576:MIRN18A microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs