MiR-382 targeting of kallikrein 5 contributes to renal inner medullary interstitial fibrosis. Physiol Genomics 2012 Feb 27;44(4):259-67
Date
12/29/2011Pubmed ID
22202692Pubmed Central ID
PMC3289118DOI
10.1152/physiolgenomics.00173.2011Scopus ID
2-s2.0-84863229877 (requires institutional sign-in at Scopus site) 75 CitationsAbstract
Previously we have shown that microRNA miR-382 can facilitate loss of renal epithelial characteristics in cultured cells. This study examined the in vivo role of miR-382 in the development of renal interstitial fibrosis in a mouse model. Unilateral ureteral obstruction was used to induce renal interstitial fibrosis in mice. With 3 days of unilateral ureteral obstruction, expression of miR-382 in the obstructed kidney was increased severalfold compared with sham-operated controls. Intravenous delivery of locked nucleic acid-modified anti-miR-382 blocked the increase in miR-382 expression and significantly reduced inner medullary fibrosis. Expression of predicted miR-382 target kallikrein 5, a proteolytic enzyme capable of degrading several extracellular matrix proteins, was reduced with unilateral ureteral obstruction. Anti-miR-382 treatment prevented the reduction of kallikrein 5 in the inner medulla. Furthermore, the protective effect of the anti-miR-382 treatment against fibrosis was abolished by renal knockdown of kallikrein 5. Targeting of kallikrein 5 by miR-382 was confirmed by 3'-untranslated region luciferase assay. These data support a completely novel mechanism in which miR-382 targets kallikrein 5 and contributes to the development of renal inner medullary interstitial fibrosis. The study provided the first demonstration of an in vivo functional role of miR-382 in any species and any organ system.
Author List
Kriegel AJ, Liu Y, Cohen B, Usa K, Liu Y, Liang MAuthor
Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
3' Untranslated RegionsAnimals
Fibrosis
Immunohistochemistry
Kallikreins
Kidney Diseases
Male
Mice
MicroRNAs
