ELK and LERK-2 in developing kidney and microvascular endothelial assembly.
ELK and LERK-2 in developing kidney and microvascular endothelial assembly.
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发表时间：
1996-12
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通讯作者：
Thomas O. Daniel;E. Stein;D. Cerretti;St John Pl;B. Robert;Dale R. Abrahamson
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作者：
Thomas O. Daniel;E. Stein;D. Cerretti;St John Pl;B. Robert;Dale R. Abrahamson
Eph家族受体酪氨酸激酶指导神经元细胞靶向、成束和细胞间聚集活性，但迄今为止，它们在哺乳动物肾脏发育中的作用尚未被探索。我们最近发现ELK（Eph样激酶）受体在培养的人肾微血管内皮细胞（HRMEC）中的表达，并表明ELK介导其在体外组装成毛细血管样结构，以响应外源性配体，LEERK-2。在这里，我们确定了ELK配体，LERK-2，在HRMEC和原始血管结构的发展小鼠肾脏的表达。ELK和LERK-2以与VEGF受体flk-1相似的模式在原始微血管的内皮祖细胞上表达。ELK LERK-2和flk-1抗原也显示在分支输尿管芽上皮上; ELK和LERK-2表达持续存在于成熟的集合管、肾小球和小动脉中。为了探索肾源性内皮细胞是否可以区分LEERK-2与血管生成性Eck配体LEERK-1（B61），以及不同来源的内皮细胞是否可以区分Eph受体配体，我们在体外毛细血管样组装试验中比较了HRMEC和人脐静脉内皮细胞（HUVEC）的反应。HRMEC内皮细胞组装毛细血管样结构响应于LERK 2，但不是LERK 1，在促进HUVEC组装响应于LERK 1，但不是LERK 2的条件下。因此，通过特异性Eph家族受体（ELK和Eck）介导的反应被来自不同血管床来源的内皮细胞区分。ELK及其配体LERK-2在表达上是时空协调的，并且可能在肾微血管的形态发生中起作用。
Eph family receptor tyrosine kinases direct neuronal cell targeting, bundling and intercellular aggregation activity, yet their role in mammalian kidney development has been unexplored to date. We recently identified expression of ELK (Eph-like kinase) receptors in cultured human renal microvascular endothelial cells (HRMEC), and showed that ELK mediates their in vitro assembly into capillary-like structures in response to the exogenous ligand, LERK-2. Here we identify expression of the ELK ligand, LERK-2, in HRMEC and in primitive vascular structures of developing murine kidney. ELK and LERK-2 are expressed on endothelial progenitor cells of primitive microvasculature in a pattern similar to that of the VEGF receptor, flk-1. ELK LERK-2 and flk-1 antigens are also displayed on the branching ureteric bud epithelium; ELK and LERK-2 expression persists in mature collecting ducts, glomeruli and arterioles. To explore whether renal-derived endothelial cells may distinguish LERK-2 from the angiogenic Eck ligand, LERK-1 (B61), and whether endothelial cells from different sources may distinguish among Eph receptor ligands, we compared HRMEC and human umbilical vein endothelial cell (HUVEC) responses in an in vitro capillary-like assembly assay. HRMEC endothelial cells assembled capillary-like structures in response to LERK-2, but not LERK-1, under conditions that promoted HUVEC to assemble in response to LERK-1, but not LERK-2. Therefore, responses mediated through specific Eph family receptors (ELK and Eck) are discriminated by endothelial cells from different vascular bed sources. ELK and its ligand, LERK-2, are spatially and temporally coordinated in expression and may function in morphogenesis of the renal microvasculature.