Expression of hypoxia-inducible transcription factors in developing human and rat kidneys
Expression of hypoxia-inducible transcription factors in developing human and rat kidneys
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DOI：
10.1038/sj.ki.5000062
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发表时间：
2006-01-01
影响因子：
19.6
通讯作者：
Eckardt, KU
中科院分区：
文献类型：
--
作者：
Bernhardt, WM;Schmitt, R;Eckardt, KU
早期肾脏发育与肾小管和血管系统的协调分支有关，缺氧已被认为是这一过程中的主要调节因素。在低氧水平下，低氧诱导转录因子（HIF）调节参与血管生成、红细胞生成和糖酵解的基因的表达。为了研究HIF在肾脏发育中的作用，我们分析了氧调节的HIF-1 α和-2 α亚基在大鼠和人肾脏发育的不同阶段的时空表达。使用双染色程序，定位的HIF靶基因产物血管内皮生长因子（VEGF）和endoglin研究与HIF α。在这两个物种中，我们发现显着的核表达HIF-1 α在髓质和皮质集合管和肾小球细胞。相比之下，HIF-2 α在更成熟的肾小球的间质细胞和管周细胞足细胞中表达。在肾小球形成和肾形成完成后，不再检测到HIF-1 α和HIF-2 α。HIF靶基因VEGF与HIF-1 α蛋白共定位于肾小球和髓质集合管。HIF-2 α与内皮相关血管生成因子内皮糖蛋白共定位。两种HIF α亚型在发育中的肾脏中以细胞特异性和时间控制的方式被激活，表明氧张力在肾发生中的调节作用。HIF-1 α似乎主要参与肾小管发生，HIF-2 α参与肾血管发生。这两种亚型都存在于肾小球发生中，可能具有协同作用。
Early kidney development is associated with the coordinated branching of the renal tubular and vascular system and hypoxia has been proposed to be a major regulatory factor in this process. Under low oxygen levels, the hypoxia-inducible transcription factor (HIF) regulates the expression of genes involved in angiogenesis, erythropoiesis and glycolysis. To investigate the role of HIF in kidney development, we analyzed the temporal and spatial expression of the oxygen regulated HIF-1 alpha and -2 alpha subunits at different stages of rat and human kidney development. Using double-staining procedures, localization of the HIF target geneproducts vascular endothelial growth factor (VEGF) and endoglin was studied in relation to HIF alpha. In both species, we found marked nuclear expression of HIF-1 alpha in medullary and cortical collecting ducts and in glomerular cells. In contrast, HIF-2 alpha was expressed in interstitial and peritubular cells podocytes of the more mature glomeruli. After completion of glomerulogenesis and nephrogenesis, HIF-1 alpha and -2 alpha were no longer detectable. The HIF-target gene VEGF colocalized with HIF-1 alpha protein in glomeruli and medullary collecting ducts. HIF-2 alpha colocalized with the endothelium-associated angiogenic factor, endoglin. Both HIF alpha isoforms are activated in the developing kidney in a cell-specific and temporally controlled manner, indicating a regulatory role of oxygen tension in nephrogenesis. HIF-1 alpha seems to be primarily involved in tubulogenesis and HIF-2 alpha in renal vasculogenesis. Both isoforms are found in glomerulogenesis, potentially having synergistic effects.