Inhibition of NF-κB-dependent Bcl-xL expression by clusterin promotes albumin-induced tubular cell apoptosis

O. Takase, A. W.M. Minto, T. S. Puri, P. N. Cunningham, A. Jacob, M. Hayashi, R. J. Quigg

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Apoptosis and inflammation, important contributors to the progression of chronic kidney disease, can be influenced by clusterin (a secreted glycoprotein that regulates apoptosis) and nuclear factor-κB (NF-κB, a transcription factor modifying the expression of inflammatory genes). We studied proteinuria-induced renal disease and its influence on clusterin-mediated apoptosis. Exposure of cultured mouse proximal tubule epithelial cells to bovine serum albumin (BSA) resulted in activation of NF-κB and activator protein-1 (AP-1) within hours followed by a decline in their activation, decreased activation of extracellular signal-regulated kinases (ERK1/2), decreased cell-associated antiapoptotic Bcl-xL protein but increased apoptosis. Clusterin progressively increased in the media over a 3 day period. Clusterin siRNA blocked protein production, increased NF-κB activation, and significantly increased cellular Bcl-xL protein, thereby reducing spontaneous and BSA-induced apoptosis. An siRNA to the NF-κB inhibitor IκBα had similar results. BSA-stimulated NF-κB activation reciprocally decreased AP-1 activity by preventing ERK1/2 phosphorylation. These in vitro studies suggest that clusterin inhibits NF-κB-mediated antiapoptotic effects by the apparent stabilization of IκBα switching from promoting inflammation to apoptosis during proteinuria.

Original languageEnglish
Pages (from-to)567-577
Number of pages11
JournalKidney international
Issue number5
Publication statusPublished - 2008 Mar



  • Apoptosis
  • Complement
  • Epithelial
  • Progression of chronic renal failure
  • Proteinuria
  • Signaling

ASJC Scopus subject areas

  • Nephrology

Cite this

Takase, O., Minto, A. W. M., Puri, T. S., Cunningham, P. N., Jacob, A., Hayashi, M., & Quigg, R. J. (2008). Inhibition of NF-κB-dependent Bcl-xL expression by clusterin promotes albumin-induced tubular cell apoptosis. Kidney international, 73(5), 567-577.