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

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

研究成果: Article査読

8 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)181-188
ページ数8
ジャーナルClinical and experimental nephrology
12
3
DOI
出版ステータスPublished - 2008 6
外部発表はい

ASJC Scopus subject areas

  • 生理学
  • 腎臓病学
  • 生理学(医学)

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