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miR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by HIF-α activation. Am J Physiol Renal Physiol 2013 May 15;304(10):F1274-82

Date

03/08/2013

Pubmed ID

23467423

Pubmed Central ID

PMC3651624

DOI

10.1152/ajprenal.00287.2012

Scopus ID

2-s2.0-84878641501   74 Citations

Abstract

Treatment with L-mimosine, which activates hypoxia-inducible factor-α (HIF-α), attenuates renal tubulointerstitial injury and improves renal function in a rat remnant kidney model. The miR-29 family of microRNAs directly targets a large number of extracellular matrix genes and reduces renal interstitial fibrosis. We analyzed microRNA expression profiles in rat remnant kidneys with or without treatment with L-mimosine. The expression of miR-29c was downregulated in rat remnant kidneys compared with sham control and significantly restored by the L-mimosine treatment. In cultured human kidney epithelial HK2 cells, cobalt chloride activated HIF-α and upregulated miR-29c expression. The upregulation of miR-29c expression was significantly attenuated by knockdown of HIF-1α or HIF-2α. Downregulation of miR-29c was associated with significant increases in interstitial fibrosis, collagen type II α1 (COL2A1) protein, and tropomyosin 1α (TPM1) protein in rat remnant kidneys and in kidneys from IgA nephropathy patients. The increases in rat remnant kidneys were attenuated by the L-mimosine treatment. COL2A1 and TPM1 were confirmed to be new, direct targets of miR-29c. In conclusion, miR-29c, an antifibrotic microRNA, is upregulated by HIF-α activation. MiR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by activation of HIF-α that attenuates fibrosis.

Author List

Fang Y, Yu X, Liu Y, Kriegel AJ, Heng Y, Xu X, Liang M, Ding X

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

Animals
Cell Line
Down-Regulation
Fibrosis
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Kidney
Kidney Diseases
Male
MicroRNAs
Mimosine
Mutagenesis, Site-Directed
Rats
Rats, Sprague-Dawley
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d