Hypoxia induces the dysfunction of human endothelial colony-forming cells via HIF-1α signaling

被引：18

作者：

He, Mengyu ^{[1
]}

Ma, Shuying ^{[1
]}

Cai, Qing ^{[1
]}

Wu, Yan ^{[2
]}

Shao, Chengjie ^{[1
]}

Kong, Hui ^{[1
]}

Wang, Hong ^{[1
]}

Zeng, Xiaoning ^{[1
]}

Xie, Weiping ^{[1
]}

机构：

[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Nanjing 210029, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Wuxi Peoples Hosp, Dept Resp Med, Wuxi 214023, Jiangsu, Peoples R China

来源：

RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY | 2018年 / 247卷

基金：

中国国家自然科学基金;

关键词：

ECFCs; Hypoxia; Proliferation; Angiogenesis; HIF-1; alpha; PULMONARY ARTERIAL-HYPERTENSION; BLOOD-VESSEL FORMATION; PROGENITOR CELLS; GROWTH-FACTOR; INDUCIBLE FACTORS; PROLIFERATION; ANGIOGENESIS; SENESCENCE; EXPRESSION; INHIBITORS;

D O I：

10.1016/j.resp.2017.09.013

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

Endothelial injury is considered as a trigger of pulmonary vascular lesions in the pathogenesis of hypoxic pulmonary hypertension (HPH). Although endothelial colony-forming cells (ECFCs) have vascular regeneration potential to maintain endothelial integrity, hypoxia-induced precise alteration in ECFCs function remains controversial. This study investigated the impact of hypoxia on human ECFCs function in vitro and the underlying mechanism. We found that hypoxia inhibited ECFCs proliferation, migration and angiogenesis. Compared with no treatment, the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha) in hypoxia-treated ECFCs was increased, with an up-regulation of p27 and a down-regulation of cyclin Dl. The over-secreted vascular endothelial growth factor (VEGF) was detected, with the imbalanced expression of fetal liver kinase 1 (flk-1) and fms related tyrosine kinase 1 (flt-1). Hypoxia-induced changes in ECFCs could be reversed by HIF-1 alpha inhibitor KC7F2. These data suggest that HIF-la holds the key in regulating ECFCs function which may open a new perspective of ECFCs in HPH management.

引用

页码：87 / 95

页数：9

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