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MiR-382 targeting of kallikrein 5 contributes to renal inner medullary interstitial fibrosis. Physiol Genomics 2012 Feb 27;44(4):259-67

Date

12/29/2011

Pubmed ID

22202692

Pubmed Central ID

PMC3289118

DOI

10.1152/physiolgenomics.00173.2011

Scopus ID

2-s2.0-84863229877   59 Citations

Abstract

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 M

Authors

Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin
Yong Liu PhD Assistant Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

3' Untranslated Regions
Animals
Fibrosis
Immunohistochemistry
Kallikreins
Kidney Diseases
Male
Mice
MicroRNAs
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d