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The inhibitory effect of chimeric decoy oligodeoxynucleotide against NF-κB and Sp1 in renal interstitial fibrosis

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An Erratum to this article was published on 23 April 2013

Abstract

The pathophysiology of chronic renal disease is characterized by a progressive loss of renal function and deposition of the extracellular matrix, leading to widespread tissue fibrosis. Much of the matrix in chronic renal disease is synthesized by interstitial myofibroblasts, recruited from resident fibroblasts and circulating precursors. These changes are believed to be derived from epithelial–mesenchymal transition (EMT) of tubuloepithelial cells. To develop a novel therapeutic approach for treating renal fibrosis, we examined the simultaneous inhibition of the transcription factors NF-κB and Sp1 in a mouse model of unilateral ureteral obstruction (UUO). To simultaneously inhibit both NF-κB and Sp1, we developed chimeric (Chi) decoy oligodeoxynucleotide (ODN) which contained binding sequences for both NF-κB and Sp1 in a single decoy molecule to enhance the effective use of decoy ODN strategy. Chi decoy ODN significantly attenuated tubulointerstitial fibrosis in a mouse model of UUO compared to scrambled decoy ODN, as demonstrated by the reduced interstitial volume, macrophage infiltration, and fibrosis-related gene expression. Interestingly, Chi decoy ODN also regulated EMT-related gene expression, leading to the inhibition of renal fibrotic changes in vivo and in vitro. The present study demonstrates the feasibility of Chi decoy ODN treatment for preventing renal fibrosis and EMT processes. This strategy might be useful to improve the clinical outcome after chronic renal disease.

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Acknowledgment

This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2009-353-E00022). This work was also supported by the grant of Research Institute of Medical Science, Catholic University of Daegu (2010).

Conflict of interest

There is no conflict of interest to disclose for any of the authors.

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Authors and Affiliations

  1. Department of Pathology, College of Medicine, Catholic University of Daegu, 3056-6 Daemyung 4-dong, Daegu, Nam-gu, 705-718, Republic of Korea

    Kyung-Hyun Kim, Ji-Hyun Park, Woo-Ram Lee & Kwan-Kyu Park

  2. Department of Urology, College of Medicine, Catholic University of Daegu, 3056-6 Daemyung 4-dong, Daegu, Nam-gu, 705-718, Republic of Korea

    Jae-Shin Park

  3. Department of Internal Medicine, Division of Nephrology, School of Medicine, Keimyung University, 194 Dongsan-dong, Daegu, Jung-gu, 700-712, Republic of Korea

    Hyun-Chul Kim

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Correspondence to Kwan-Kyu Park.

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Kim, KH., Park, JH., Lee, WR. et al. The inhibitory effect of chimeric decoy oligodeoxynucleotide against NF-κB and Sp1 in renal interstitial fibrosis. J Mol Med 91, 573–586 (2013). https://doi.org/10.1007/s00109-012-0972-2

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  • DOI: https://doi.org/10.1007/s00109-012-0972-2

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