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学科主题基础医学
GTP cyclohydrolase I prevents diabetic-impaired endothelial progenitor cells and wound healing by suppressing oxidative stress/thrombospondin-1
Tie, Lu2; Chen, Lu-Yuan3; Chen, Dan-Dan1; Xie, He-Hui1; Channon, Keith M.4; Chen, Alex F.1
关键词guanosine triphosphate cyclohydrolase I endothelial progenitor cells oxidative stress wound healing diabetes
刊名AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
2014-05-01
DOI10.1152/ajpendo.00696.2013
306期:10页:E1120-E1131
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism ; Physiology
研究领域[WOS]Endocrinology & Metabolism ; Physiology
关键词[WOS]NITRIC-OXIDE SYNTHASE ; GENE-TRANSFER ; THROMBOSPONDIN-1 ; TETRAHYDROBIOPTERIN ; MOBILIZATION ; STRESS ; DYSFUNCTION ; RECEPTOR ; DISEASE ; MICE
英文摘要

Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic refractory wounds. Endothelial nitric oxide synthase (eNOS), which critically regulates the mobilization and function of EPCs, is uncoupled in diabetes due to decreased cofactor tetrahydrobiopterin (BH4). We tested whether GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme of BH4 synthesis, preserves EPC function in type 1 diabetic mice. Type 1 diabetes was induced in wild-type (WT) and GTPCH I transgenic (Tg-GCH) mice by intraperitoneal injection of streptozotocin (STZ). EPCs were isolated from the peripheral blood and bone marrow of WT, Tg-GCH, and GTPCH I-deficient hph-1 mice. The number of EPCs was significantly lower in STZ-WT mice and hph-1 mice and was rescued in STZ Tg-GCH mice. Furthermore, GTPCH I overexpression improved impaired diabetic EPC migration and tube formation. EPCs from WT, Tg-GCH, and STZ-Tg-GCH mice were administered to diabetic excisional wounds and accelerated wound healing significantly, with a concomitant augmentation of angiogenesis. Flow cytometry measurements showed that intracellular nitric oxide (NO) levels were reduced significantly in STZ-WT and hph-1 mice, paralleled by increased superoxide anion levels; both were rescued in STZ-Tg-GCH mice. Western blot analysis revealed that thrombospondin-1 (TSP-1) was significantly upregulated in the EPCs of STZ-WT mice and hph-1 mice and suppressed in STZ-treated Tg-GCH mice. Our results demonstrate that the GTPCH I/BH4 pathway is critical to preserve EPC quantity, function, and regenerative capacity during wound healing in type 1 diabetic mice at least partly through the attenuation of superoxide and TSP-1 levels and augmentation of NO level.

语种英语
WOS记录号WOS:000336906300003
项目编号2014CB542400 ; 81130004 ; 81370359 ; 913392019 ; 81373405 ; 30901803 ; 30900519 ; 81370429
资助机构National Basic Research Program (973 Program) ; National Science Foundation of China
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65625
专题北京大学基础医学院_药理学系
北京大学基础医学院
作者单位1.Cent S Univ, Xiangya Hosp 3, Ctr Clin Pharmacol, Changsha 410013, Hunan, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pharmacol, Beijing 100871, Peoples R China
3.Guangdong Gen Hosp, Dept Cardiol, Guangzhou, Guangdong, Peoples R China
4.Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England
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Tie, Lu,Chen, Lu-Yuan,Chen, Dan-Dan,et al. GTP cyclohydrolase I prevents diabetic-impaired endothelial progenitor cells and wound healing by suppressing oxidative stress/thrombospondin-1[J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM,2014,306(10):E1120-E1131.
APA Tie, Lu,Chen, Lu-Yuan,Chen, Dan-Dan,Xie, He-Hui,Channon, Keith M.,&Chen, Alex F..(2014).GTP cyclohydrolase I prevents diabetic-impaired endothelial progenitor cells and wound healing by suppressing oxidative stress/thrombospondin-1.AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM,306(10),E1120-E1131.
MLA Tie, Lu,et al."GTP cyclohydrolase I prevents diabetic-impaired endothelial progenitor cells and wound healing by suppressing oxidative stress/thrombospondin-1".AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 306.10(2014):E1120-E1131.
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