A molecular and genetic analysis of renalglomerular capillary development.
A molecular and genetic analysis of renalglomerular capillary development.
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DOI：
10.1023/a:1018357116559
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发表时间：
1997-01-01
期刊：
影响因子：
9.8
通讯作者：
Woolf, A S
中科院分区：
文献类型：
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作者：
Loughna, S;Hardman, P;Woolf, A S
成人肾脏是高度血管化的，接受约20%的心输出量，但肾小球毛细血管的发育模式尚不完全清楚。肾形成初期，凝聚后肾间质不含毛细血管。然而，在本研究中，我们在未诱导的小鼠E11后肾间质和来自该组织的细胞系中检测了血管内皮生长因子（VEGF） mRNA和蛋白。此外，E11间质表达了内皮前体细胞（VEGFR-1/Flt-1、VEGFR-2/Flk-1和Tie-1）标记的受体酪氨酸激酶的转录本。在转基因小鼠中，当没有血管通畅时，在E11肾间质中发现了表达Tie1/ lacz的细胞。此外，在中间中胚层凝聚形成后肾间质中也检测到类似的转基因表达模式。将Tie-1/LacZ E11后肾移植到野生型小鼠肾原皮质后，在供肾组织中发现表达转基因的肾小球毛细血管袢。相比之下，肾小球Tie-1/ lacz阳性血管在器官培养的雏形中从未发育。我们假设内皮前体存在于小鼠肾形成的初始阶段，当实验条件与体内后肾相似时，内皮前体分化并经历形态发生，形成肾小球毛细血管。
The adult kidney is highly vascular and receives about 20% of the cardiac output, yet the mode of development of the glomerular capillaries is not fully understood. At the inception of nephrogenesis the condensed metanephric mesenchyme contains no patent capillaries. However, in this current study we detected vascular endothelial growth factor (VEGF) mRNA and protein in uninduced mouse E11 metanephric mesenchyme and in cell lines from this tissue. Moreover, transcripts for receptor tyrosine kinases which are markers of endothelial precursors (VEGFR-1/Flt-1, VEGFR-2/Flk-1 and Tie-1) were expressed by the E11 mesenchyme. In transgenic mice, Tie1/LacZ-expressing cells were identified in E11 renal mesenchyme when patent vessels were absent. Moreover, a similar pattern of transgene expression was detected within intermediate mesoderm condensing to form metanephric mesenchyme. When Tie-1/LacZ E11 metanephroi were transplanted into the nephrogenic cortex of wild-type mice, transgene-expressing capillary loops were detected in glomeruli developing in donor tissue. In contrast, glomerular Tie-1/LacZ-positive vessels never developed in rudiments in organ culture. We postulate that endothelial precursors are present at the inception of the mouse nephrogenesis, and these differentiate and undergo morphogenesis into glomerular capillaries when experimental conditions resemble those found in the metanephros in vivo.