[HTML][HTML] Gene transfer of truncated IκBα prevents tubulointerstitial injury
O Takase, J Hirahashi, A Takayanagi, A Chikaraishi… - Kidney international, 2003 - Elsevier
Kidney international, 2003•Elsevier
Gene transfer of truncated IκBα prevents tubulointerstitial injury. 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 …
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 …
Gene transfer of truncated IκBα prevents tubulointerstitial injury.
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.
Elsevier
