Targeted deletion of Dicer from proximal tubules protects against renal ischemia-reperfusion injury.
MicroRNAs are endogenous, noncoding, small RNAs that regulate expression and function of genes, but little is known about regulation of microRNA in the kidneys under normal or pathologic states. Here, we generated a mouse model in which the proximal tubular cells lack Dicer, a key enzyme for microRNA production. These mice had normal renal function and histology under control conditions despite a global downregulation of microRNAs in the renal cortex; however, these animals were remarkably resistant to renal ischemia-reperfusion injury (IRI), showing significantly better renal function, less tissue damage, lower tubular apoptosis, and improved survival compared with their wild-type littermates. Microarray analysis showed altered expression of specific microRNAs during renal IRI. Taken together, these results demonstrate evidence for a pathogenic role of Dicer and associated microRNAs in renal IRI.
Wei
Qingqing
Q
Department of Cellular Biology and Anatomy, Medical College of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, USA. qwei@mail.mcg.edu
Bhatt
Kirti
K
He
Hong-Zhi
HZ
Mi
Qing-Sheng
QS
Haase
Volker H
VH
Dong
Zheng
Z
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism*; D055786:Gene Knockout Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism*; D043244:Ribonuclease III
D035683:MicroRNAs; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases