Diminished NF-κB activation and PDGF-B expression in glomerular endothelial cells subjected to chronic shear stress

Eudora Eng*, Barbara J. Ballermann

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

We tested the hypothesis that in endothelial cells, chronic arterial shear stress represses both the transactivator nuclear factor-κB (NF-κB) and subsequent platelet-derived growth factor (PDGF)-B gene transcription. Bovine aortic endothelial (BAE) and glomerular capillary endothelial (GEN) cells were subjected to chronic (9 days) arterial shear stress (10 dyne/cm2). Chronic shear stress reduced PDGF-B transcripts in BAE cells by 59 ± 23% compared to controls, and by 70 ± 14% in GEN cells. While PDGF-B mRNA levels were not significantly changed in BAE cells subjected to acute (4 h) shear stress, in GEN cells PDGF-B transcript abundance fell by 59 ± 3%. PDGF-B mRNA stability was unchanged. We investigated the possibility that these effects were due to decreased nuclear NF-κB. NF-κB levels were much lower in nuclei of chronic shear stress-treated cells compared to controls. This represents classical inactivation of NF-κB since cytoplasmic NF-κB/I-κB (the inhibitory protein of NF-κB) levels were elevated in shear stress-treated cells. Further supporting NF-κB regulation of PDGF-B, activation of NF-κB by interleukin (IL)-1β resulted in increased PDGF-B transcript levels. Treatment of cells with MG-132, an inhibitor of NF-κB activation, resulted in a dramatic decrease in basal PDGF-B transcript levels, and essentially abrogated the response to IL-1β. Thus, repression of NF-κB activation in endothelial cells by shear stress decreases PDGF-B gene expression, while activators of NF-κB increase PDGF-B transcription.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalMicrovascular Research
Volume65
Issue number3
DOIs
StatePublished - Jan 1 2003

Keywords

  • Differentiation
  • Glomerular endothelial cell
  • NF-κB
  • PDGF-B
  • Transcriptional regulation

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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