PMID- 22835519 OWN - NLM STAT- MEDLINE DCOM- 20130426 LR - 20231002 IS - 1095-9319 (Electronic) IS - 0026-2862 (Linking) VI - 84 IP - 3 DP - 2012 Nov TI - LIF maintains progenitor phenotype of endothelial progenitor cells via Kruppel-like factor 4. PG - 270-7 LID - S0026-2862(12)00147-1 [pii] LID - 10.1016/j.mvr.2012.07.005 [doi] AB - 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 Kruppel-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. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Li, Xiaoxia AU - Li X AD - Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 China. lixiaoxia@bjmu.edu.cn FAU - Song, Yimeng AU - Song Y FAU - Wang, Dawei AU - Wang D FAU - Fu, Chenglai AU - Fu C FAU - Zhu, Zhenjiu AU - Zhu Z FAU - Han, Yingying AU - Han Y FAU - Li, Chenghong AU - Li C FAU - Wang, Nanping AU - Wang N FAU - Zhu, Yi AU - Zhu Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120723 PL - United States TA - Microvasc Res JT - Microvascular research JID - 0165035 RN - 0 (Antigens, CD34) RN - 0 (KLF4 protein, human) RN - 0 (Kruppel-Like Factor 4) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (Leukemia Inhibitory Factor) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Antigens, CD34/biosynthesis MH - Cell Differentiation MH - Cell Proliferation MH - Endothelial Cells/*cytology MH - Fetal Blood/cytology MH - Flow Cytometry/methods MH - *Gene Expression Regulation MH - Humans MH - Kruppel-Like Factor 4 MH - Kruppel-Like Transcription Factors/*metabolism MH - Leukemia Inhibitory Factor/*metabolism MH - Microcirculation MH - Phenotype MH - Phosphorylation MH - Stem Cells/*cytology MH - Vascular Endothelial Growth Factor A/metabolism EDAT- 2012/07/28 06:00 MHDA- 2013/04/27 06:00 CRDT- 2012/07/28 06:00 PHST- 2011/09/09 00:00 [received] PHST- 2012/06/22 00:00 [revised] PHST- 2012/07/16 00:00 [accepted] PHST- 2012/07/28 06:00 [entrez] PHST- 2012/07/28 06:00 [pubmed] PHST- 2013/04/27 06:00 [medline] AID - S0026-2862(12)00147-1 [pii] AID - 10.1016/j.mvr.2012.07.005 [doi] PST - ppublish SO - Microvasc Res. 2012 Nov;84(3):270-7. doi: 10.1016/j.mvr.2012.07.005. Epub 2012 Jul 23.