Mesenchymal expression of vascular endothelial growth factors D and A defines vascular patterning in developing lung

Mesenchymal expression of vascular endothelial growth factors D and A defines vascular patterning in developing lung
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DOI:
10.1002/dvdy.10095
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发表时间:
2002-06-01
影响因子:
2.5
通讯作者:
Akeson, AL
Akeson, AL
中科院分区:
生物学3区
文献类型:
--
作者:
Greenberg, JM;Thompson, FY;Akeson, AL

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肺具有特定的血管模式要求,以在出生时进行有效的气体交换,包括气道、血管和淋巴管的对齐。血管内皮生长因子(VEGF)是血管发育的有效效应因子。我们研究了VEGF-D和特异性VEGF-A亚型在肺发育各个阶段的时空表达。VEGF-D仅由间充质的钙粘蛋白-11阳性细胞表达,在胚胎第13.5天(E)首次检测到,这是一个活跃的血管发生时期。其同源受体VEGFR-3在E11.5-E14.5天较早时在血管和淋巴管中检测到,并且在E17.5天较晚时仅在淋巴管中检测到。VEGF-A在整个肺发育过程中在间充质中表达,并且在器官发生中途也由上皮表达。在E14之前,VEGF-A的主要形式是可溶性同种型,VEGF-A120和164。直到E14.5,扩张气道顶端的上皮细胞才表达VEGF-A,包括VEGF-A188,一种对细胞外基质具有高亲和力的同种型。我们的研究结果表明,独特的时间和空间表达的VEGF-D和特定的VEGF-A亚型在肺发育过程中,并建议这些相关的因素有不同的功能,在血管和淋巴图案的肺。(C)2002 Wiley-Liss,Inc.
The lung has specific vascular patterning requirements for effective gas exchange at birth, including alignment of airways and blood vessels and lymphatic vessels. Vascular endothelial growth factors (VEGF) are potent effectors of vascular development. We examined the temporal and spatial expression of VEGF-D and specific VEGF-A isoforms at each stage of lung development. VEGF-D, expressed only by cadherin-11-positive cells of the mesenchyme, is first detected at embryonic day (E) 13.5, a period of active vasculogenesis. VEGFR-3, its cognate receptor, is detected earlier on days E11.5 to E14.5, in both blood vessels and lymphatic vessels and later, on day E17.5, in only lymphatic vessels. VEGF-A is expressed in the mesenchyme throughout lung development and also by the epithelium midway through organogenesis. Before E14, the predominant forms of VEGF-A are the soluble isoforms, VEGF-A120 and 164. Not until E14.5 do epithelial cells at the tips of expanding airways express VEGF-A, including VEGF-A188, an isoform with high affinity for extracellular matrix. Our results demonstrate unique temporal and spatial expression of VEGF-D and specific VEGF-A isoforms during lung development and suggest these related factors have distinct functions in vascular and lymphatic patterning of the lung. (C) 2002 Wiley-Liss, Inc.