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NF-κB-dependent genes induced by proteinuria and identified using DNA microarrays

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Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

A close correlation has been shown between tubulointerstitial (TI) injury and the outcome of renal dysfunction, and nuclear factor-kappaB (NFκB) has been shown to play a key role in proteinuria-induced TI injury. To explore the molecular mechanisms of the proteinuria-induced TI injury further, we have analyzed renal gene expression with DNA microarrays, with and without specific inhibition of NF-κB in the proximal tubules.

Methods

Unilaterally nephrectomized rats loaded with bovine serum albumin (BSA) were used as a model of proteinuric renal injury. Renal NF-κB activation was inhibited by gene transfer of the truncated form of IκBα (inhibitor of NF-κB) via the injection of a recombinant adenovirus vector into the renal artery, an method established in a previous study. Total RNA was extracted from the kidney and analyzed with a DNA microarrays containing 1081 genes.

Results

Renal NF-κB activation and TI injury in BSA-loaded proteinuric rats were inhibited by the gene transfer of the truncated form of IκBα. DNA microarray analysis revealed 45 up-regulated genes and six down-regulated genes in the proteinuric rats, and expression of 23 of these 51 genes was significantly altered by NF-κB inhibition. Among these 23 genes, we focused on clusterin and confirmed the results of microarray analysis by Western blotting and PCR.

Conclusion

In this study, 23 genes of 51 proteinuria-related genes were regulated by NF-κB activation, suggesting that some of these genes may serve as target molecules for the treatment of progressive TI injury.

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Acknowledgments

This work was supported in part by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Health Science Research Grants from the Ministry of Health, Labour and Welfare, and a Grant for Fundamental Research Program for Advanced Medical Apparatus Undertaken in Cooperation with Medical and Engineering Researchers from the New Energy and Industrial Technology Development Organization (NEDO). Portions of this work were presented at the 36th Annual Meeting and Scientific Exposition of the American Society of Nephrology, San Diego, California, USA and at the 47th Annual Meeting of the Japanese Society of Nephrology, Tochigi, Japan.

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Correspondence to Matsuhiko Hayashi.

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Takase, O., Marumo, T., Hishikawa, K. et al. NF-κB-dependent genes induced by proteinuria and identified using DNA microarrays. Clin Exp Nephrol 12, 181–188 (2008). https://doi.org/10.1007/s10157-008-0038-5

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  • DOI: https://doi.org/10.1007/s10157-008-0038-5

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