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

Abstract

BackgroundEndothelial 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 resultsCo-treatment with LIF and VEGF (100ng/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. ConclusionsLIF 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.