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Status |
Public on Feb 01, 2013 |
Title |
Gene expression profiling in endothelial precursor cells of patients protected from microvascular complications |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
In this study, we examined the impact of modulating the TGF-β/PAI-1 axis in CD34+ cells function from diabetic patients and controls. Using gene array studies, we found that diabetics, protected from microvascular complications despite suboptimal glycemic control, had reduced level of TGF- β1 and PAI-1 transcripts in their CD34+ cells compared to age, sex, duration and degree of glycemic control -matched diabetics with microvascular complications. Treatment with neutralizing antibody to TGF- β1 in murine hematopoietic stem cells (HSC) enhanced in vivo repopulation potential of these cells in bone marrow transplantation; reduced the time required for cell division of single cells, increased survival of the progenitor cells and reduced TGF-β1 expression. TGF- β1 phosphorodiamidate morpholino oligomers (PMO) treatment reduced PAI-1 mRNA expression in diabetic (p<0.01) and non-diabetic (p=0.05) CD34+ cells. Inhibition of PAI-1 promoted CD34+ cell proliferation and migration in vitro.Targetting TGFβ-1/PAI-1 system offers a promising therapeutic strategy for restoring vascular reparative function in diabetic CD34+ cells and hematopoietic stem cells, enhancing key functions needed for cell therapy.
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Overall design |
Peripheral blood from either age matched controls (n=5), diabetics with long standing poorly controlled diabetes and no microvascular complications (n=4), and diabetics with long-standing poorly controlled diabetes with severe microvascular complications (n=5) was obtained and CD34+ cells were isolated. RNA was extracted followed by AffyNugen amplification, and the cDNA was probed to Human RSTA Affymetrix 2.0 chip
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Contributor(s) |
Hazra S, Stepps V, Bhatwadekar AD, Boulton ME, Higgins PJ, Nikonova EV, Pepine CJ, Thut C, Finney EM, Sitnicka E, Iversen P, Ruscetti F, Stone DJ, Bartelmez SH, Grant MB |
Citation missing |
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Submission date |
Jan 31, 2013 |
Last update date |
Jul 09, 2014 |
Contact name |
Ashay Dilip Bhatwadekar |
Organization name |
University of Florida
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Department |
Pharmacology and Therapeutics
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Street address |
1600 SW Archer Road
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City |
Gainesville |
State/province |
FL |
ZIP/Postal code |
32610 |
Country |
USA |
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Platforms (1) |
GPL10379 |
Rosetta/Merck Human RSTA Custom Affymetrix 2.0 microarray [HuRSTA-2a520709] |
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Samples (14)
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GSM1074874 |
IR-E-Long standing diabetes with no complications (1.75ng 1st Round AMP) |
GSM1074875 |
IR-D-Long standing diabetes with no complications (4.3ng 1st Round AMP) |
GSM1074876 |
GN-C-Long standing diabetes with microvascular disease |
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Relations |
BioProject |
PRJNA188223 |
Supplementary file |
Size |
Download |
File type/resource |
GSE43950_RAW.tar |
78.5 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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