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Enhancing the function of CD34(+) cells by targeting plasminogen activator inhibitor-1.

Authors :
Sugata Hazra
Valerie Stepps
Ashay D Bhatwadekar
Sergio Caballero
Michael E Boulton
Paul J Higgins
Elena V Nikonova
Carl J Pepine
Catherine Thut
Eva M Finney
David J Stone
Stephen H Bartelmez
Maria B Grant
Source :
PLoS ONE, Vol 8, Iss 11, p e79067 (2013)
Publication Year :
2013
Publisher :
Public Library of Science (PLoS), 2013.

Abstract

Previously, we showed that transient inhibition of TGF- β1 resulted in correction of key aspects of diabetes-induced CD34(+) cell dysfunction. In this report, we examine the effect of transient inhibition of plasminogen activator inhibitor-1 (PAI-1), a major gene target of TGF-β1 activation. Using gene array studies, we examined CD34(+) cells isolated from a cohort of longstanding diabetic individuals, free of microvascular complications despite suboptimal glycemic control, and found that the cells exhibited reduced transcripts of both TGF-β1 and PAI-1 compared to age, sex, and degree of glycemic control-matched diabetic individuals with microvascular complications. CD34(+) cells from diabetic subjects with microvascular complications consistently exhibited higher PAI-1 mRNA than age-matched non-diabetic controls. TGF- β1 phosphorodiamidate morpholino oligo (PMO) reduced PAI-1 mRNA in diabetic (p

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
8
Issue :
11
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.46a5af6d5ea341dbaded9bbbcf0726cd
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0079067