Hypoxia-induced proliferation of tissue-resident endothelial progenitor cells in the lung.

Hypoxia-induced proliferation of tissue-resident endothelial progenitor cells in the lung.
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缺氧诱导肺内组织驻留内皮祖细胞的增殖。

DOI:
10.1152/ajplung.00243.2014
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发表时间:
2014
期刊:
Am J Physiol Lung Cell Mol Physiol.
影响因子:
--
通讯作者:
Tatsumi K
Tatsumi K
中科院分区:
--
文献类型:
--
作者:
Nishimura R;Kawasaki T;Sekine A;Suda R;Urushibara T;Suzuki T;Takayanagi S;Terada J;Sakao S;Tatsumi K

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暴露于缺氧诱导组成肺血管壁的细胞的结构和功能表型的变化,从大血管到大多数外周血管。内皮祖细胞(EPCs)可能参与血管内皮修复。在肺微循环中发现具有高增殖潜力的常驻EPCs。然而,它们的潜在位置、标识和职能作用尚未明确确定。我们研究了是否常驻EPCs或骨髓(BM)来源的EPCs在肺血管内皮细胞(PVECs)的缺氧反应中发挥主要作用。小鼠暴露于缺氧。PVEC的数量短暂减少,然后在缺氧动物中增加。在缺氧条件下1周,显着的溴脱氧尿苷掺入检测PVEC。缺氧1周后,PVEC中可见Ki 67阳性细胞,尤其是毛细血管。为了阐明增殖内皮细胞的起源,我们使用表达绿色荧光蛋白(GFP)的BM嵌合小鼠。GFP阳性PVEC的百分比在BM移植小鼠的缺氧过程中是低的且恒定的,这表明在缺氧条件下BM衍生的细胞在肺中的植入很少。缺氧动物的PVEC中CD 34表达增加,表明缺氧诱导的EPC或干/祖细胞标志物的基因表达和细胞表面抗原。从缺氧小鼠分离的PVEC显示集落和管形成能力。本研究表明,低氧可诱导PVEC增殖,其来源可能是组织中的内皮祖细胞。
Exposure to hypoxia induces changes in the structure and functional phenotypes of the cells composing the pulmonary vascular wall from larger to most peripheral vessels. Endothelial progenitor cells (EPCs) may be involved in vascular endothelial repair. Resident EPCs with a high proliferative potential are found in the pulmonary microcirculation. However, their potential location, identification, and functional role have not been clearly established. We investigated whether resident EPCs or bone marrow (BM)-derived EPCs play a major role in hypoxic response of pulmonary vascular endothelial cells (PVECs). Mice were exposed to hypoxia. The number of PVECs transiently decreased followed by an increase in hypoxic animals. Under hypoxic conditions for 1 wk, prominent bromodeoxyuridine incorporation was detected in PVECs. Some Ki67-positive cells were detected among PVECs after 1 wk under hypoxic conditions, especially in the capillaries. To clarify the origin of proliferating endothelial cells, we used BM chimeric mice expressing green fluorescent protein (GFP). The percentage of GFP-positive PVECs was low and constant during hypoxia in BM-transplanted mice, suggesting little engraftment of BM-derived cells in lungs under hypoxia. Proliferating PVECs in hypoxic animals showed increased expression of CD34, suggesting hypoxia-induced gene expression and cell surface antigen of EPC or stem/progenitor cells markers. Isolated PVECs from hypoxic mice showed colony- and tube-forming capacity. The present study indicated that hypoxia could induce proliferation of PVECs, and the origin of these cells might be tissue-resident EPCs.
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