LIF maintains progenitor phenotype of endothelial progenitor cells via Krüppel-like factor 4

Xiaoxia Li, Yimeng Song, Dawei Wang, Chenglai Fu, Zhenjiu Zhu, Yingying Han, Chenghong Li, Nanping Wang, Yi Zhu

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Endothelial progenitor cells (EPCs) participate in post-natal vasculogenesis. Maintaining the preliminary progenitor phenotype and good proliferation capacity of EPCs is key to their use in treating cardiovascular ischemic diseases. However, transcriptional regulation in EPCs remains largely unknown. We investigated the effect of leukemia inhibitory factor (LIF) combined with vascular endothelial growth factor (VEGF) on EPCs and the potential roles of Krüppel-like transcription factors (KLFs). Methods and results: Co-treatment with LIF and VEGF (100 ng/ml each) (V+L) could increase EPC colony-forming units and CD34 expression, which reflects the EPC progenitor phenotype and alleviated differentiation of EPCs. The effect was associated with Akt activation and increased expression of KLF4. Upregulation of KLF4 induced by V+L could be inhibited by transfection with dominant-negative Akt adenovirus. Furthermore, overexpression of KLF4 in EPCs enhanced the expression of CD34 and alleviated cell differentiation but did not increase the phosphorylation of Akt. Conclusions: LIF combined with VEGF can maintain the preliminary, progenitor phenotype of EPCs and alleviate cell differentiation by upregulating KLF4, which may provide new insights into transcriptional regulation in EPCs.

Original languageEnglish (US)
Pages (from-to)270-277
Number of pages8
JournalMicrovascular Research
Volume84
Issue number3
DOIs
StatePublished - Nov 1 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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