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Clinical and Experimental Nephrology

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01.06.2008 | Original Article

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

verfasst von: Osamu Takase, Takeshi Marumo, Keiichi Hishikawa, Toshiro Fujita, Richard J. Quigg, Matsuhiko Hayashi

Erschienen in: Clinical and Experimental Nephrology | Ausgabe 3/2008

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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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Titel: NF-κB-dependent genes induced by proteinuria and identified using DNA microarrays
verfasst von: Osamu Takase
Takeshi Marumo
Keiichi Hishikawa
Toshiro Fujita
Richard J. Quigg
Matsuhiko Hayashi
Publikationsdatum: 01.06.2008
Verlag: Springer Japan
Erschienen in: Clinical and Experimental Nephrology / Ausgabe 3/2008
Print ISSN: 1342-1751
Elektronische ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-008-0038-5

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

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Methods

Results

Conclusion

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