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Title: High glucose attenuates VEGF expression in rat multipotent adult progenitor cells in association with inhibition of JAK2/STAT3 signaling
Authors: Liu, Zehao ×
Lei, Minxiang
Jiang, Yuehua
Hao, Hong
Chu, Ling
Xu, Jian
Luo, Min
Verfaillie, Catherine
Zweier, Jay L
Liu, Zhenguo #
Issue Date: Sep-2009
Publisher: Carol Davila University Press
Series Title: Journal of Cellular and Molecular Medicine vol:13 issue:9B pages:3427-3436
Abstract: Background: This study was to investigate the effect of high glucose (HG) on VEGF expression in bone marrow stem cells and JAK2/STAT-3 signaling. Methods: Adult rat bone marrow multipotent progenitor cells (rMAPCs) were cultured to evaluate VEGF expression (both mRNA and protein) with or without exposure to HG for up to 48 hrs using RT-PCR and ELISA. JAK2 and STAT3 phosphorylation in rMAPCs was analyzed by Western blotting. Results: With cells in normal media, VEGF mRNA level after 24 hrs of culture was significantly increased by 15 times over baseline (day 0) with detectable level of VEGF protein intracellularly using immunofluorescence staining. While there was no measurable VEGF in the media after 24 hrs of culture, a significant amount of VEGF was detected in the media after 48 hrs of incubation. VEGF expression was associated with constitutive activation of JAK2 and STAT3 in rMAPCs. However, VEGF mRNA level was significantly reduced without detectable VEGF in the media when rMAPCs exposed to HG for 48 hrs. Tyrosine-phosphorylation of JAK2 and STAT3 and nuclear translocation of phosphorylated STAT3 were significantly decreased in the cells exposed to HG for 48 hrs. When JAK2 and STAT3 phosphorylation was blocked by the selective inhibitor AG490, VEGF mRNA level was significantly decreased in rMAPCs in normal media by 80% with no detectable VEGF in the media. VEGF expression was significantly suppressed in rMAPCs cultured in HG media that was further reduced by AG490. Conclusion: VEGF expression in rMAPCs is impaired by HG possibly through inhibition of JAK2/STAT3 signaling.
URI: 
ISSN: 1582-4934
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdepartemental Stem Cell Institute (-)
Department of Materials Engineering - miscellaneous
× corresponding author
# (joint) last author

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