Transcription factor Krüppel-like factor 2 plays a vital role in endothelial colony forming cells differentiation

Yimeng Song, Xiaoxia Li, Dawei Wang, Chenglai Fu, Zhenjiu Zhu, Ming Hui Zou, Yi Zhu

Research output: Contribution to journalArticlepeer-review

Abstract

Aims Endothelial colony forming cells (ECFCs) participate in post-natal vasculogenesis.We previously reported that vascular endothelial growth factor (VEGF) promotes human ECFC differentiation through AMP-activated protein kinase (AMPK) activation. However, the mechanisms underlying transcriptional regulation of ECFC differentiation still remain largely elusive. Here, we investigated the role of transcription factor Krüppel-like factor 2 (KLF2) in the regulation of ECFC function. Methods and results Human ECFCs were isolated from cord blood and cultured. Treatment with VEGF significantly increased endothelial markers in ECFCs and their capacity for migration and tube formation. The mRNA and protein levels of KLF2 were also significantly up-regulated. This up-regulation was abrogated by AMPK inhibition or by knockdown of KLF2 with siRNA. Furthermore, adenovirus-mediated overexpression of KLF2 promoted ECFC differentiation by enhancing expression of endothelial cell markers, reducing expression of progenitor cell markers, and increasing the capacity for tube formation in vitro, indicating the important role of KLF2 in ECFC-mediated angiogenesis. Histone deacetylase 5 (HDAC5) was phosphorylated byAMPKactivity induced by VEGFand theAMPKagonist AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide). In vivo angiogenesis assay revealed that overexpression of KLF2 in bone-marrowderived pro-angiogenic progenitor cells promoted vessel formation when the cells were implanted in C57BL/6 mice. Conclusion Up-regulation of KLF2 by AMPK activation constitutes a novel mechanism of ECFC differentiation, and may have therapeutic value in the treatment of ischaemic heart disease.

Original languageEnglish (US)
Pages (from-to)514-524
Number of pages11
JournalCardiovascular research
Volume99
Issue number3
DOIs
StatePublished - Aug 1 2013

Keywords

  • AMPK
  • Differentiation
  • Endothelial progenitor cells
  • Krüppel-like factor 2
  • VEGF

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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