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High glucose enhances TGF-β1 expression in rat bone marrow stem cells via ERK1/2-mediated inhibition of STAT3 signaling.
MedLine Citation:
PMID:  22285838     Owner:  NLM     Status:  Publisher    
AIMS: This study was to investigate the effect of high glucose (HG) on TGF-β1 expression and the underlying mechanisms in bone marrow stem cells. MAIN METHODS AND KEY FINDINGS: Rat bone marrow multipotent adult progenitor cells (MAPCs) were cultured in normal (5.5mM d-glucose) and HG media (25.5mM d-glucose) for up to 14days. l-Glucose (20mM plus 5.5mM d-glucose) was used as high osmolarity control. TGF-β1 expression was evaluated using quantitative RT-PCR, ELISA, and immunofluorescence staining for its mRNA and protein level in the cells and in the conditioned media. The expression and activation of ERK1/2 and STAT3 were examined in MAPCs cultured in HG media with Western blot. Measurable level of TGF-β1 was detected in the cells cultured in normal media. TGF-β1 expression was substantially increased in MAPCs after 36h of culture in HG media with over 20-fold increase in the mRNA and 5-fold increase in protein level over control. Interestingly, ERK1/2 phosphorylation was significantly increased in MAPCs cultured in HG media, while in STAT3 (Tyr705), not STAT3 (Ser727), phosphorylation was dramatically decreased. Treatment of cells with the specific MEK1 inhibitor PD98059 or U0126 suppressed ERK1/2 phosphorylation and TGF-β1 expression, and completely restored the level of STAT3 (Tyr705) phosphorylation in MAPCs cultured in HG media. Treatment of the cells with the specific STAT3 phosphorylation inhibitor AG490 significantly blocked STAT3 (Tyr705) phosphorylation and increased TGF-β1 expression without change in ERK1/2 phosphorylation in MPACs. SIGNIFICANCE: HG increased TGF-β1 expression through inhibition of STAT3 (Tyr705) by enhanced ERK1/2 signaling in MAPCs.
Min Luo; Zehao Liu; Guohua Chen; Hong Hao; Tiewei Lu; Yuqi Cui; Minxiang Lei; Catherine M Verfaillie; Zhenguo Liu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-20
Journal Detail:
Title:  Life sciences     Volume:  -     ISSN:  1879-0631     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Department of Endocrinology, Xiangya Hospital of Central South University, Changsha, Hunan, China; Davis Heart & Lung Research Institute and Division of Cardiovascular Medicine, The Ohio State University Medical Center, Columbus, OH, USA.
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