NF-κB-dependent increase in intrarenal angiotensin II induced by proteinuria

Osamu Takase, Takeshi Marumo, Naohiko Imai, Junichi Hirahashi, Atsushi Takayanagi, Keiichi Hishikawa, Matsuhiko Hayashi, Nobuyoshi Shimizu, Toshiro Fujita, Takao Saruta

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Background. Intrarenal activation of the renin-angiotensin system has been suggested to play a pivotal role in the progression of various renal diseases, but the regulation of each component has not been fully clarified. We investigated the roles of nuclear factor κB (NF-κB) activation in the intrarenal renin-angiotensin system changes induced by proteinuria. Methods. We used unilaterally nephrectomized rats loaded with bovine serum albumin as a model of proteinuric renal injury. Renal NF-κB activation was inhibited by gene transfer of the truncated form of IκBα via injection of a recombinant adenovirus vector into the renal artery, as we reported previously. Results. Inhibition of renal NF-κB activation attenuated the increases in intrarenal angiotensinogen protein (2.0-fold in rats with protein overloading and saline injection to 1.3-fold in rats with protein overloading and injection of a truncated form of IκBα) and angiotensin II (1.8-fold to 1.2-fold), and angiotensinogen mRNA. The increases in angiotensin-converting enzyme (ACE) and angiotensin II receptor type 2 were unaffected by NF-κB inhibition. The expression of ACE2, an enzyme that metabolizes angiotensins I and II, was decreased by 37%, and NF-κB inhibition abolished the decrease. Immunohistochemical analysis revealed that the angiotensinogen and ACE2 expression changes occurred mainly in proximal tubule cells (i.e., the target of adenoviral gene transfer). Conclusion. These results indicate that proteinuria induces an increase in renal angiotensin II in an NF-κB-dependent manner. Induction of angiotensinogen and decrease in ACE2 levels may be involved in this NF-κB-dependent increase in angiotensin II.

Original languageEnglish
Pages (from-to)464-473
Number of pages10
JournalKidney international
Volume68
Issue number2
DOIs
Publication statusPublished - 2005 Aug

Keywords

  • Adenovirus
  • Angiotensin-converting enzyme
  • Angiotensin-converting enzyme 2
  • Angiotensinogen
  • Gene transfer
  • NF-κB
  • Proteinuria

ASJC Scopus subject areas

  • Nephrology

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