Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts.

Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts.
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有证据表明表达 flk-1 的胚胎肾细胞是内在的血管生成血管细胞。

DOI:
10.1152/ajprenal.1996.271.3.f744
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发表时间:
1996
期刊:
The American journal of physiology.
影响因子:
--
通讯作者:
Abrahamson,DR
Abrahamson,DR
中科院分区:
--
文献类型:
--
作者:
Robert,B;StJohn,PL;Hyink,DP;Abrahamson,DR

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肾小球毛细血管束被认为起源于外源性血管的新生生长。然而,我们发现,当胚胎第12天(E12)小鼠的肾脏在培养中保持6天,然后移植到成年转基因ROSA26宿主小鼠的前房(携带β-半乳糖苷酶转基因),移植物内的肾小球内皮细胞主要来自固有的肾脏来源。为了识别潜在的内皮前体,我们用抗血管内皮生长因子受体Flk-1的抗体免疫肾脏。大量表达Flk-1的离散细胞散布在E12和新生肾脏的肾源性间充质中,随着发育,这些细胞集中在微血管、肾小球血管间隙和肾小球束中。在成人中,Flk-1在肾小球中弱表达,但在其他地方不表达。为了检测Flk-1阳性细胞建立肾小球的能力,将E12个肾脏移植到成年和新生儿ROSA26宿主的肾皮质中。移植到成人体内的肾小球很少含有宿主来源的内皮细胞,而大部分移植到新生儿体内的肾小球含有宿主细胞。移植物来源的细胞在新生宿主的肾皮质中形成的血管中被发现,但在成年宿主中没有。我们的发现表明,表达Flk-1的胚胎肾细胞是血管母细胞,通过血管生成产生微血管和肾小球。
Renal glomerular capillary tufts have been believed to arise from angiogenic ingrowth of extrinsic vessels. We found, however, that when embryonic day 12 (E12) mouse kidneys were maintained in culture for 6 days and then grafted into anterior eye chambers of adult transgenic ROSA26 host mice (which carry the beta-galactosidase transgene), glomerular endothelial cells within the grafts were predominantly of intrinsic, kidney origin. To identify potential endothelial precursors, we immunolabled kidneys with antibodies against the vascular endothelial growth factor receptor, flk-1. Numerous discrete cells expressing flk-1 were scattered throughout the nephrogenic mesenchyme of both E12 and newborn kidneys, and with development these cells became concentrated in microvessels, glomerular vascular clefts, and glomerular tufts. In adults, flk-1 was weakly expressed in glomeruli but absent elsewhere. To examine abilities of flk-1-positive cells to establish glomeruli, E12 kidneys were grafted into kidney cortices of adult and newborn ROSA26 hosts. Grafts into adults resulted in few glomeruli containing host-derived endothelium, whereas a majority of glomeruli grafted into newborns contained host cells. Cells of graft origin were found in vessels forming in renal cortices of newborn hosts, but not in adults. Our findings indicate that embryonic kidney cells expressing flk-1 are angioblasts that create microvessels and glomeruli by vasculogenesis.