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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)181-188
Number of pages8
JournalClinical and experimental nephrology
Volume12
Issue number3
DOIs
Publication statusPublished - 2008 Jun 1

Keywords

  • Apoptosis
  • Clusterin
  • DNA microarray
  • Gene transfer
  • NF-κB
  • Proteinuria
  • Proximal tubular cells

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'NF-κB-dependent genes induced by proteinuria and identified using DNA microarrays'. Together they form a unique fingerprint.

  • Cite this

    Takase, O., Marumo, T., Hishikawa, K., Fujita, T., Quigg, R. J., & Hayashi, M. (2008). NF-κB-dependent genes induced by proteinuria and identified using DNA microarrays. Clinical and experimental nephrology, 12(3), 181-188. https://doi.org/10.1007/s10157-008-0038-5