Gene transfer of truncated IκBκ prevents tubulointerstitial injury

Osamu Takase, Junichi Hirahashi, Atsushi Takayanagi, Akihiro Chikaraishi, Takeshi Marumo, Yuri Ozawa, Matsuhiko Hayashi, Nobuyoshi Shimizu, Takao Saruta

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70 Citations (Scopus)

Abstract

Background. Severe proteinuria not only indicates the presence of progressive glomerular disease, but also causes tubular epithelial cells to produce inflammatory mediators leading to tubulointerstitial (TI) injury. We investigated the role of nuclear factor-κB (NF-κB) in tubular epithelial cells in the development of proteinuria-induced TI injury. Methods. To specifically inhibit NF-κB activation, a recombinant adenovirus vector expressing a truncated form of IκBα (AdexIκBδN) was injected into renal arteries of protein-overloaded rats, a model of TI injury characterized by infiltration of mononuclear cells and fibrosis. Results. Activation of NF-κB in the renal cortex, observed in protein-overloaded rats treated with a control vector, recombinant lacZ adenovirus, was prevented in AdexIκBΔN-injected rats. Microscopic examination revealed AdexIκBΔN treatment to markedly attenuate proteinuria-induced TI injury. Increased immunostaining of vascular cell adhesion molecule-1, transforming growth factor-β, and fibronectin in TI lesions also was suppressed by AdexIκBΔN injection. Conclusions. These findings provide evidence of the critical role of NF-κB activation in TI injury and suggest the therapeutic potential of adenovirus-mediated IκBΔN gene transfer into the kidney as a means of interrupting the process of TI damage.

Original languageEnglish
Pages (from-to)501-513
Number of pages13
JournalKidney international
Volume63
Issue number2
DOIs
Publication statusPublished - 2003 Jan 1

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Keywords

  • Adenovirus
  • Inflammation
  • Nuclear factor-κB
  • Progressive renal disease
  • Proteinuria
  • Tubulointerstitial injury

ASJC Scopus subject areas

  • Nephrology

Cite this

Takase, O., Hirahashi, J., Takayanagi, A., Chikaraishi, A., Marumo, T., Ozawa, Y., Hayashi, M., Shimizu, N., & Saruta, T. (2003). Gene transfer of truncated IκBκ prevents tubulointerstitial injury. Kidney international, 63(2), 501-513. https://doi.org/10.1046/j.1523-1755.2003.00781.x