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 MMESH terms used to index this publication - Major topics in bold
3' Untranslated RegionsAnimals
Fibrosis
Immunohistochemistry
Kallikreins
Kidney Diseases
Male
Mice
MicroRNAs
