TY - JOUR
T1 - LIF maintains progenitor phenotype of endothelial progenitor cells via Krüppel-like factor 4
AU - Li, Xiaoxia
AU - Song, Yimeng
AU - Wang, Dawei
AU - Fu, Chenglai
AU - Zhu, Zhenjiu
AU - Han, Yingying
AU - Li, Chenghong
AU - Wang, Nanping
AU - Zhu, Yi
N1 - Funding Information:
We thank Dr. Weijuan Yao at Peking University Health Science Center for carefully reading the manuscript and kind comments. This work was supported in part by grants from the National Natural Science Foundation of China (Nos. 81070113 , 30600209 , 30630032 , 30821001 ), the Major National Basic Research Grant of China (No. 2010CB912504 ).
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/11
Y1 - 2012/11
N2 - 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.
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 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.
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U2 - 10.1016/j.mvr.2012.07.005
DO - 10.1016/j.mvr.2012.07.005
M3 - Article
C2 - 22835519
AN - SCOPUS:84868115082
SN - 0026-2862
VL - 84
SP - 270
EP - 277
JO - Microvascular Research
JF - Microvascular Research
IS - 3
ER -