Identification of a microRNA signature of renal ischemia reperfusion injury.
Renal ischemia reperfusion injury (IRI) is associated with significant morbidity and mortality. Given the importance of microRNAs (miRNAs) in regulating gene expression, we examined expression profiles of miRNAs following renal IRI. Global miRNA expression profiling on samples prepared from the kidneys of C57BL/6 mice that underwent unilateral warm ischemia revealed nine miRNAs (miR-21, miR-20a, miR-146a, miR-199a-3p, miR-214, miR-192, miR-187, miR-805, and miR-194) that are differentially expressed following IRI when compared with sham controls. These miRNAs were also differently expressed following IRI in immunodeficient RAG-2/common gamma-chain double-knockout mice, suggesting that the changes in expression observed are not significantly influenced by lymphocyte infiltration and therefore define a lymphocyte-independent signature of renal IRI. In vitro studies revealed that miR-21 is expressed in proliferating tubular epithelial cells (TEC) and up-regulated by both cell-intrinsic and -extrinsic mechanisms resulting from ischemia and TGF-beta signaling, respectively. In vitro, knockdown of miR-21 in TEC resulted in increased cell death, whereas overexpression prevented cell death. However, overexpression of miR-21 alone was not sufficient to prevent TEC death following ischemia. Our findings therefore define a molecular fingerprint of renal injury and suggest miR-21 may play a role in protecting TEC from death.
Godwin
Jonathan G
JG
Transplantation Research Center, Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Ge
Xupeng
X
Stephan
Kristin
K
Jurisch
Anke
A
Tullius
Stefan G
SG
Iacomini
John
J
D000818:Animals; D016923:Cell Death / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007668:Kidney / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D020011:Protective Agents; D015427:Reperfusion Injury / Q000235:genetics*
C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D020011:Protective Agents