MiR-382 targeting of kallikrein 5 contributes to renal inner medullary interstitial fibrosis.

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.

• Authors: Alison J Kriegel, Yong Liu, Brett Cohen, Kristie Usa, Youhua Liu, Mingyu Liang
• Journal: Physiological genomics (Physiol Genomics) Vol. 44 Issue 4 Pg. 259-67 (Feb 27 2012) ISSN: 1531-2267 [Electronic] United States
• PMID: 22202692 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• MicroRNAs
• Kallikreins
• Klk5 protein, mouse

Topics

• 3' Untranslated Regions (genetics)
• Animals
• Fibrosis (genetics, metabolism)
• Immunohistochemistry
• Kallikreins (genetics, metabolism)
• Kidney Diseases (genetics, metabolism)
• Male
• Mice
• MicroRNAs (genetics, metabolism)