title: LIF maintains progenitor phenotype of endothelial progenitor cells via Krüppel-like factor 4.
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).
  
  
  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.
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 China. lixiaoxia@bjmu.edu.cn
authors: Xiaoxia
authors: X
authors: Li
authors: Yimeng
authors: Y
authors: Song
authors: Dawei
authors: D
authors: Wang
authors: Chenglai
authors: C
authors: Fu
authors: Zhenjiu
authors: Z
authors: Zhu
authors: Yingying
authors: Y
authors: Han
authors: Chenghong
authors: C
authors: Li
authors: Nanping
authors: N
authors: Wang
authors: Yi
authors: Y
authors: Zhu
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis; D002454:Cell Differentiation; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D008833:Microcirculation; D010641:Phenotype; D010766:Phosphorylation; D013234:Stem Cells / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D053605:Leukemia Inhibitory Factor; D042461:Vascular Endothelial Growth Factor A