Embryonic lethality in Dear gene-deficient mice:: new player in angiogenesis
Embryonic lethality in Dear gene-deficient mice:: new player in angiogenesis
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DOI：
10.1152/physiolgenomics.00144.2005
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发表时间：
2005-11-17
影响因子：
4.6
通讯作者：
Ruiz-Opazo, N
中科院分区：
文献类型：
--
作者：
Herrera, VLM;Ponce, LRB;Ruiz-Opazo, N
Dear基因缺陷小鼠的胚胎致死性：血管生成的新参与者Physiol Genomics 23：257 - 268，2005; doi：10.1152/physiolgenomics. 00144.2005. - 在Dahl S/JR（HS）大鼠品系中，内皮素-1/血管紧张素II双重受体（Dear）以同等亲和力结合内皮素-1（ET-1）和血管紧张素II（ANG II）。为了阐明其生理意义的背景下，多种受体亚型和不同的ET-1和血管紧张素II的功能，跨越血压调节，肿瘤增殖和血管生成，我们的特点是小鼠亲爱的和Dear缺陷小鼠。与ET-1、ANG II和所有其他ET-1和ANG II受体的无效突变模型不同，Dear（-/-）缺陷导致血管生成受损、神经上皮发育失调和胚胎12.5天的胚胎致死。有趣的是，小鼠Dear不结合ANG II，类似于Dahl R/JR（HS）大鼠Dear，但以相同的亲和力结合ET-1和血管内皮生长因子（VEGF）信号肽（VEGFsp），这表明VEGFsp具有推定的新的多功能性，以及协调VEGF诱导和Dear介导的途径的简约机制。与其发育性血管生成作用一致，Dear抑制导致雌性Dear（+/-）/C57BL6（BC10）小鼠中B16-F10黑色素瘤细胞诱导的皮下肿瘤的肿瘤生长减少，但雄性（3.5月龄）和Sprague-Dawley雌性大鼠（3 - 6.5月龄）中Cs-127辐射诱导的原位乳腺肿瘤的肿瘤生长没有减少。总之，数据确定亲爱的作为一个新的球员在血管生成过程中的发展下游，和非冗余的，VEGF介导的途径，以及肿瘤血管生成的一个假定的调制器内的性别特异性的范例。
Embryonic lethality in Dear gene-deficient mice: new player in angiogenesis. Physiol Genomics 23: 257-268, 2005; doi: 10.1152/physiolgenomics. 00144.2005. - The dual endothelin-1/angiotensin II receptor ( Dear) binds endothelin-1 (ET-1) and angiotensin II (ANG II) with equal affinities in the Dahl S/JR(HS) rat strain. To elucidate its physiological significance within the context of multiple receptor isoforms and diverse ET-1 and ANG II functions spanning blood pressure regulation, tumor proliferation, and angiogenesis, we characterized mouse Dear and Dear-deficient mice. Unlike null mutant models of ET-1, ANG II, and all other ET-1 and ANG II receptors, Dear(-/-) deficiency results in impaired angiogenesis, dysregulated neuroepithelial development, and embryonic lethality by embryonic day 12.5. Interestingly, mouse Dear does not bind ANG II, similar to Dahl R/JR(HS) rat Dear, but binds ET-1 and vascular endothelial growth factor ( VEGF) signal peptide (VEGFsp) with equal affinities, suggesting a putative novel multifunction for VEGFsp and a parsimonious mechanism for coordination of VEGF-induced and Dear-mediated pathways. Consistent with its developmental angiogenic role, Dear inhibition results in decreased tumor growth in B16-F10 melanoma cell-induced subcutaneous tumor in female Dear(+/-)/C57BL6(BC10) mice, but not in males (age 3.5 mo), and in Cs-127 radiation-induced orthotopic mammary tumors in Sprague-Dawley female rats ( age range 3-6.5 mo). Altogether, the data identify Dear as a new player in angiogenesis during development downstream to, and nonredundant with, VEGF-mediated pathways, as well as a putative modulator of tumor angiogenesis acting within a gender-specific paradigm.