Skip to main content

Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells.

Publication ,  Journal Article
Zhu, S; Evans, S; Yan, B; Povsic, TJ; Tapson, V; Goldschmidt-Clermont, PJ; Dong, C
Published in: Circulation
November 18, 2008

BACKGROUND: Endothelial progenitor cells (EPCs) contribute to vascular regeneration/repair and thus may protect against scleroderma vasculopathy. We aimed to determine whether circulating EPCs were reduced in scleroderma, whether scleroderma sera could induce EPC apoptosis, and, if so, what the underlying apoptotic signaling pathway was. METHODS AND RESULTS: Circulating EPC levels were quantified in 54 patients with scleroderma and 18 healthy control subjects by colony-forming unit assay and flow cytometry, which revealed markedly decreased EPC levels in scleroderma patients relative to healthy subjects. Substantial apoptosis was detected in EPCs after culturing in the presence of scleroderma sera compared with normal sera. Intriguingly, depletion of the IgG fraction from scleroderma sera completely abolished the apoptotic effects. Furthermore, scleroderma sera inhibited the activation/phosphorylation of Akt, which in turn suppressed the phosphorylation and degradation of forkhead transcription factor FKHRL1 (FOXO3a), resulting in the upregulation of apoptotic protein Bim. siRNA-mediated FOXO3a and Bim knockdown substantially reduced scleroderma serum-induced EPC apoptosis. Importantly, Bim expression and baseline apoptosis were increased in EPCs freshly isolated from scleroderma patients relative to that obtained from healthy subjects. CONCLUSIONS: Scleroderma serum-induced EPC apoptosis is mediated chiefly by the Akt-FOXO3a-Bim pathway, which may account, at least in part, for the decreased circulating EPC levels in scleroderma patients.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

November 18, 2008

Volume

118

Issue

21

Start / End Page

2156 / 2165

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Stem Cells
  • Serum
  • Scleroderma, Systemic
  • Regeneration
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Middle Aged
  • Membrane Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhu, S., Evans, S., Yan, B., Povsic, T. J., Tapson, V., Goldschmidt-Clermont, P. J., & Dong, C. (2008). Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells. Circulation, 118(21), 2156–2165. https://doi.org/10.1161/CIRCULATIONAHA.108.787200
Zhu, Shoukang, Sarah Evans, Bin Yan, Thomas J. Povsic, Victor Tapson, Pascal J. Goldschmidt-Clermont, and Chunming Dong. “Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells.Circulation 118, no. 21 (November 18, 2008): 2156–65. https://doi.org/10.1161/CIRCULATIONAHA.108.787200.
Zhu S, Evans S, Yan B, Povsic TJ, Tapson V, Goldschmidt-Clermont PJ, et al. Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells. Circulation. 2008 Nov 18;118(21):2156–65.
Zhu, Shoukang, et al. “Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells.Circulation, vol. 118, no. 21, Nov. 2008, pp. 2156–65. Pubmed, doi:10.1161/CIRCULATIONAHA.108.787200.
Zhu S, Evans S, Yan B, Povsic TJ, Tapson V, Goldschmidt-Clermont PJ, Dong C. Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells. Circulation. 2008 Nov 18;118(21):2156–2165.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

November 18, 2008

Volume

118

Issue

21

Start / End Page

2156 / 2165

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Stem Cells
  • Serum
  • Scleroderma, Systemic
  • Regeneration
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Middle Aged
  • Membrane Proteins