检索结果-内蒙古大学图书馆

Up-regulation of vascular endothelial growth factor receptor Flt-1 after endothelial denudation:: role of transcription factor Egr-1

引用

BLOOD 2000年第11期95卷 3387-3395页

作者： Vidal, F Aragonés, J Alfranca, A de Landázuri, MO Univ Autonoma Puebla Hosp Princesa Serv Inmunol Madrid 28006 Spain

Vascular endothelial growth factor (VEGF) is highly expressed in vascular remodeling processes and accelerates reendothelialization after mechanical denudation, Two VEGF tyrosine kinase receptors have been reported-fms-like-tyrosine kinase-1 (Flt-1) and kinase domain region (KDR), Little is known about the regulation of the expression of these receptors after vascular injury. Herein, we have analyzed the expression of Flt-1 after mechanical denudation of primary cultures of endothelial cells, which has been considered a useful in vitro model to study endothelium responses to vascular injury. After denudation, the Flt-1 protein and mRNA levels are clearly up-regulated, and transient transfection experiments showed a strong induction of the flt-1 promoter-dependent transcription. Analysis of the flt-1 promoter sequence revealed the presence of a putative binding site for the early growth response factor-1 (Egr-1) at positions -24 to -16, Electrophoretic mobility shift and supershift assays showed that Egr-1 was able to bind to this DNA sequence, and cotransfection of the flt-1 promoter reporter plasmid with an Egr-1 expression vector resulted in enhancement of its transcriptional activity. Furthermore, the mutation of the Egr-1 binding site markedly reduced the denudation-induced flt-1 promoter activity, These data demonstrate that Flt-1 is up-regulated after endothelial denudation and that Egr-1 plays a relevant role in this process. (Blood, 2000;95:3387-3395) (C) 2000 by The American Society of Hematology.

关键词：结合部位细胞核/代谢细胞培养的 DNA结合蛋白质类/遗传学 DNA结合蛋白质类/代谢早期生长反应蛋白质1 内皮血管/细胞学内皮血管/生理学即早蛋白质类动力学萤光素酶类/遗传学肌平滑血管/细胞学肌平滑血管/生理学启动区(遗传学) 原癌基因蛋白质类/遗传学原癌基因蛋白质类/代谢 RNA 信使/遗传学受体蛋白质酪氨酸激酶类/遗传学受体蛋白质酪氨酸激酶类/代谢受体生长因子/遗传学重组蛋白质类/代谢转录因子/遗传学转录因子/代谢转录遗传转染脐静脉增量调节血管内皮生长因子受体1 人类

来源：评论

学校读者我要写书评

暂无评论

New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis

引用

JOURNAL OF MEDICINAL CHEMISTRY 2000年第12期43卷 2310-2323页

作者： Bold, G Altmann, KH Frei, J Lang, M Manley, PW Traxler, P Wietfeld, B Brüggen, J Buchdunger, E Cozens, R Ferrari, S Furet, P Hofmann, F Martiny-Baron, G Mestan, J Rösel, J Sills, M Stover, D Acemoglu, F Boss, E Emmenegger, R Lässer, L Masso, E Roth, R Schlachter, C Vetterli, W Wyss, D Wood, JM NOVARTIS Pharma AG Oncol Res CH-4002 Basel Switzerland NOVARTIS Pharma AG Proc Res CH-4002 Basel Switzerland Tumor Biol Ctr Inst Mol Med D-79106 Freiburg Germany

The sprouting of new blood vessels, or angiogenesis, is necessary for any solid tumor to grow large enough to cause life-threatening disease. Vascular endothelial growth factor (VEGF) is one of the key promoters of tumor induced angiogenesis. VEGF receptors, the tyrosine kinases Flt-1 and KDR, are expressed on vascular endothelial cells and initiate angiogenesis upon activation by VE GF. 1-Anilino-(4-pyridylmethyl)-phthalazines, such as CGP 79787D (or PTK787 / ZK222584), reversibly inhibit Flt-1 and KDR with IC50 values < 0.1 mu M CGP 79787D also blocks the VEGF-induced receptor autophosphorylation in CHO cells ectopically expressing the KDR receptor (ED50 = 34 nM). Modification of the 1-anilino moiety afforded derivatives with higher selectivity for the VEGF receptor tyrosine kinases Flt-1 and KDR compared to the related receptor tyrosine kinases PDGF-R and c-Kit. Since these 1-anilino-(4-pyridylmethyl)phthalazines are orally well absorbed, these compounds qualify for further profiling and as candidates for clinical evaluation.

关键词：投药口服血管生成抑制剂/化学合成血管生成抑制剂/化学血管生成抑制剂/药代动力学血管生成抑制剂/药理学苯胺化合物/化学合成苯胺化合物/化学苯胺化合物/药代动力学苯胺化合物/药理学生物利用度 CHO细胞细胞系仓鼠亚科酶抑制剂/化学合成酶抑制剂/化学酶抑制剂/药代动力学酶抑制剂/药理学模型分子肿瘤/血液供给新生血管化病理性磷酰化酞嗪类/化学合成酞嗪类/化学酞嗪类/药代动力学酞嗪类/药理学原癌基因蛋白质类/拮抗剂和抑制剂吡啶类受体蛋白质酪氨酸激酶类/拮抗剂和抑制剂受体蛋白质酪氨酸激酶类/遗传学受体生长因子/拮抗剂和抑制剂受体生长因子/遗传学受体血管内皮生长因子构效关系转染血管内皮生长因子受体1 动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia

引用

AMERICAN JOURNAL OF PATHOLOGY 2000年第3期156卷 965-976页

作者： Marti, HH Bernaudin, M Bellail, A Schoch, HJ Euler, M Petit, E Risau, W Max Planck Inst Physiol & Clin Res Dept Mol Cell Biol D-61231 Bad Nauheim Germany Univ Caen CNRS UMR 6551 F-14032 Caen France

We investigated the hypothesis that hypoxia induces angiogenesis and thereby may counteract the detrimental neurological effects associated with stroke. Forty-eight to seventy-two hours after permanent middle cerebral artery occlusion we found a strong increase in the number of newly formed vessels at the border of the infarction. Using the hypoxia marker nitroimidazole EF5, we detected hypoxic cells in the ischemic border of the neocortex. Expression of vascular endothelial growth factor (VEGF), which is the main regulator of angiogenesis and is inducible by hypoxia, was strongly up-regulated in the ischemic border, at times between 6 and 24 hours after occlusion. in addition, both VEGF receptors (VEGFRs) were up-regulated at the border after 48 hours and later in the ischemic core. Finally, the two transcription factors, hypoxia-inducible factor-1 (HIF-1) and HIF-2, known to be involved in the regulation of VEGF and VEGFR gene expression, were increased in the ischemic border after 72 hours, suggesting a regulatory function for these factors. These results strongly suggest that the VEGF/VEGFR system, induced by hypoxia, leads to the growth of new vessels after cerebral ischemia, Exogenous support of this natural protective mechanism might lead to enhanced survival after stroke.

关键词：缺氧/并发症缺氧/代谢缺氧/病理学抗原 CD31/代谢脑缺血/并发症脑缺血/代谢脑缺血/病理学 DNA/分析 DNA引物/化学 DNA结合蛋白质类/代谢疾病模型动物内皮生长因子/遗传学内皮生长因子/代谢缺氧诱导因子1 缺氧诱导因子1 α亚基免疫组织化学原位杂交 Ki-67抗原/代谢淋巴因子/遗传学淋巴因子/代谢新生血管化病理性/病因学新生血管化病理性/代谢新生血管化病理性/病理学核蛋白质类/代谢肽起始因子类/代谢原癌基因蛋白质类/遗传学原癌基因蛋白质类/代谢 RNA 信使/代谢受体蛋白质酪氨酸激酶类/遗传学受体蛋白质酪氨酸激酶类/代谢受体生长因子/遗传学受体生长因子/代谢受体血管内皮生长因子逆转录聚合酶链反应转录因子/生物合成增量调节血管内皮生长因子A 血管内皮生长因子受体1 血管内皮生长因子类动物小鼠

来源：评论

学校读者我要写书评

暂无评论

Amniotic fluid-soluble vascular endothelial growth factor receptor-1 in preeclampsia

引用

OBSTETRICS AND GYNECOLOGY 2000年第3期95卷 353-357页

作者： Vuorela, P Helske, S Hornig, C Alitalo, K Weich, H Halmesmäki, E Univ Helsinki Cent Hosp Dept Obstet & Gynecol Helsinki 00029 Finland Div Mol Biotechnol Dept Gene Regulat & Differentiat Braunschweig Germany Univ Helsinki Haartman Inst Mol & Canc Biol Lab FIN-00014 Helsinki Finland

Objective: To measure the levels of the soluble receptor for the potent angiogenic agent vascular endothelial growth factor (VEGF) in amniotic fluid (AF) in healthy and complicated pregnancies, and compare them with levels of erythropoietin, another factor upregulated by hypoxia. Methods: We assessed amniotic fluid from the second (n = 35, gestational weeks 14-19) and third (n = 29) trimesters of healthy women, and from the third trimesters of preeclamptic (n = 22) and diabetic women with (n = 11) or without preeclampsia (n = 34) and from women with fetal growth restriction (FGR) (n = 14) for soluble VEGF receptor-1 (VEGFR-1) by enzyme-linked immunosorbent assay. Results: In early normal pregnancy, AF-soluble VEGFR-1 levels were higher (median 22 ng/mL, range 2.3-29.5 ng/mL) than in the third trimester (median 13 ng/mL, range 0.5-32 ng/mL;P < .05). In preeclamptic women during the third trimester, levels were higher (median 20 ng/mL, range 10.5-37 ng/mL;P < .05) than healthy controls. The lowest third-trimester levels were in diabetic women (median 11 ng/mL, range 0.5-27 ng/mL). In women with preeclampsia and diabetes, AF-soluble VEGFR-1 levels remained lower (median 13, range 6-32 ng/mL;P < .05) than in women with preeclampsia alone. Amniotic fluid levels of soluble VEGFR-1 in women with FGR (median 19.5 ng/mL, range 5-40 ng/mL) did not statistically differ from those of controls. The AF levels of soluble VEGFR-1 did not correlate with those of erythropoietin. Soluble VEGFR-1 was clearly detectable (median 14 ng/mL, range 9-22 ng/mL) in culture media from placental biopsies (n = 20). Conclusion: Preeclampsia is associated with increased levels of soluble VEGFR-1, which are independent of erythropoietin, another hypoxia-inducible factor. (Obstet Gynecol 2000;95:353-7. (C) 2000 by The American College of Obstetricians and Gynecologists.).

关键词：羊水/化学酶联免疫吸附测定胎儿生长迟缓/代谢先兆子痫/代谢妊娠中期妊娠末期糖尿病患者妊娠/代谢原癌基因蛋白质类/分析受体蛋白质酪氨酸激酶类/分析受体生长因子/分析血管内皮生长因子受体1 女(雌)性人类妊娠

来源：评论

学校读者我要写书评

暂无评论

Identification of substituted 3-[(4,5,6,7-tetrahydro-1H-indol-2-yl)methylene]-1,3-dihydroindol-2-ones as growth factor receptor inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rβ tyrosine kinases

引用

JOURNAL OF MEDICINAL CHEMISTRY 2000年第14期43卷 2655-2663页

作者： Sun, L Tran, N Liang, CX Hubbard, S Tang, F Lipson, K Schreck, R Zhou, Y McMahon, G Tang, C SUGEN Inc San Francisco CA 94080 USA NYU Med Ctr Skirball Inst Biomol Med New York NY 10016 USA NYU Med Ctr Dept Pharmacol New York NY 10016 USA

A series of new 3-substituted indolin-2-ones containing a tetrahydroindole moiety was developed as specific inhibitors of receptor tyrosine kinases associated with VEGF-R, FGF-R, and PDGF-R growth factor receptors. These compounds were evaluated for their inhibitory properties toward VEGF-R2 (Flk-1/KDR), FGF-R1, PDGF-R beta, p60(c-Src), and EGF-R tyrosine kinases and their ability to inhibit growth factor-dependent cell proliferation. Structure-activity relationships of this new pharmacophore have been determined at the level of kinase inhibition. Compounds containing a propionic acid moiety at the C-3' position of the tetrahydroindole ring represented the most potent indolin-2-ones to inactivate the VEGF, FGF, and PDGF receptor kinases. The inhibitory activities of 9d against VEGF-R2 (Flk-1), 9h against FGF-R1, and 9b against PDGF-R beta were 4, 80, and 4 nM, respectively. However, all of these compounds were inactive when tested against the EGF-R tyrosine kinase. Compounds 9a and 9b represented the most potent inhibitors of these classes to inhibit both biochemical kinase and growth factor-dependent cell proliferation for these three targets. In addition, compound 9a was cocrystallized with the catalytic domain of FGF-R1 providing evidence to explain the structure-activity relationship results. This study has provided evidence to support the potential of these new tyrosine kinase inhibitors for the treatment of angiogenesis and other growth factor-related diseases including human cancers.

关键词：抗肿瘤药/化学合成抗肿瘤药/化学抗肿瘤药/药理学细胞分裂/药物作用细胞系结晶学 X线酶抑制剂/化学合成酶抑制剂/化学酶抑制剂/药理学吲哚类/化学合成吲哚类/化学吲哚类/药理学半数抑制浓度模型分子磷酰化丙酸盐类/化学合成丙酸盐类/化学丙酸盐类/药理学原癌基因蛋白质类/拮抗剂和抑制剂受体蛋白质酪氨酸激酶类/拮抗剂和抑制剂受体血小板源生长因子β/拮抗剂和抑制剂受体生长因子/拮抗剂和抑制剂受体血管内皮生长因子构效关系酪氨酸/代谢血管内皮生长因子受体1 动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

Early induction of angiogenetic signals in gliomas of GFAP-v-src transgenic mice

引用

AMERICAN JOURNAL OF PATHOLOGY 1999年第2期154卷 581-590页

作者： Theurillat, JP Hainfellner, J Maddalena, A Weissenberger, J Aguzzi, A Univ Zurich Hosp Dept Pathol Inst Neuropathol CH-8091 Zurich Switzerland

Angiogenesis is a prerequisite for solid tumor growth. Glioblastoma multiforme, the most common malignant brain tumor, is characterized by extensive vascular proliferation. We previously showed that transgenic mice expressing a GFAP-v-src fusion gene in astrocytes develop low-grade astrocytomas that progressively evolve into hypervascularized glioblastomas, Here, we examined whether tumor progression triggers angiogenetic signals. We found abundant transcription of vascular endothelial growth factor (VEGF) in neoplastic astrocytes at surprisingly early stages of tumorigenesis, VEGF and v-src expression patterns were not identical, suggesting that VEGF activation was not only dependent on v-src. Late-stage gliomas showed perinecrotic VEGF up-regulation similarly to human glioblastoma, Expression patterns of the endothelial angiogenic receptors flt-1, flk-1, tie-1, and tie-2 were similar to those described in human gliomas, but flt-1 was expressed also in neoplastic astrocytes, suggesting an autocrine role in tumor growth. In. crossbreeding experiments, hemizygous ablation of the tumor suppressor genes Rb and p53 had no significant effect on the expression of VEGF, flt-1, flk-1, tie-1, and tie-2, Therefore, expression of angiogenic signals is an early event during progression of GFAP-v-src tumors and precedes hypervascularization. Given the close similarities in the progression pattern between GFAP-v-src and human gliomas, the present results suggest that these mice may provide a useful tool for antiangiogenic therapy research.

关键词：人工基因融合星形细胞/代谢星形细胞/病理学星形细胞瘤/遗传学星形细胞瘤/代谢星形细胞瘤/病理学脑肿瘤/遗传学脑肿瘤/代谢脑肿瘤/病理学繁殖内皮生长因子/遗传学内皮生长因子/代谢基因视网膜母细胞瘤/遗传学基因 p53/遗传学基因 src/遗传学神经胶质原纤维酸性蛋白质/遗传学淋巴因子/遗传学淋巴因子/代谢小鼠转基因新生血管化病理性/遗传学新生血管化病理性/代谢新生血管化病理性/病理学原癌基因蛋白质类/遗传学原癌基因蛋白质类/代谢 RNA 信使/生物合成受体蛋白质酪氨酸激酶类/遗传学受体蛋白质酪氨酸激酶类/代谢受体 TIE-1 受体 TIE-2 受体细胞表面/遗传学受体细胞表面/代谢受体生长因子/遗传学受体生长因子/代谢受体 TIE 受体血管内皮生长因子信号传导血管内皮生长因子A 血管内皮生长因子受体1 血管内皮生长因子类动物女(雌)性男(雄)性小鼠

来源：评论

学校读者我要写书评

暂无评论

Urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia: implications for capillary-like tube formation in a fibrin matrix

引用

BLOOD 2000年第8期96卷 2775-2783页

作者： Kroon, ME Koolwijk, P van der Vecht, B van Hinsbergh, VWM TNO PG Gaubius Lab NL-2301 CE Leiden Netherlands Vrije Univ Amsterdam Inst Cardiovasc Res Amsterdam Netherlands

Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix. hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth factor (VEGF) together with tumor necrosis factor-alpha (TNF-alpha) formed 2- to 3-fold more tubular structures under hypoxic conditions than in normoxic (20% oxygen) conditions. In both conditions the in-growth of capillary like tubular structures into fibrin required cell-bound urokinase-type plasminogen activator (uPA) and plasmin activities. The hypoxia-induced increase in tube formation was accompanied by a decrease in uPA accumulation in the conditioned medium. This decrease in uPA level was completely abolished by uPA receptor-blocking antibodies. During hypoxic culturing uPA receptor activity and messenger RNA (mRNA) were indeed increased. This increase and, as a consequence, an increase in plasmin formation contribute to the hypoxia-induced stimulation of tube formation. A possible contribution of VEGF-A to the increased formation under hypoxic conditions is unlikely because there was no increased VEGF-A expression detected under hypoxic conditions, and the hypoxia-induced tube formation by FGF-2 and TNF-or was not inhibited by soluble VEGFR-1 (sVEGFR-1), or by antibodies blocking VEGFR-2, Furthermore, although the alpha (v)-integrin subunit was enhanced by hypoxia, blocking antibodies against alpha (v)beta (3)- and alpha (v)beta (5)-integrins had no effect on hypoxia-induced tube formation. Hypoxia increases uPA association and the angiogenic response of human endothelial cells in a fibrin matrix;the increase in the uPA receptor is an important determinant in this process, (C) 2000 by The American Society of Hematology.

关键词：受体细胞表面/生物合成受体细胞表面/遗传学受体生长因子/拮抗剂和抑制剂受体生长因子/免疫学受体血管内皮生长因子受体玻连蛋白/拮抗剂和抑制剂受体玻连蛋白/免疫学肿瘤坏死因子α/药理学尿纤溶酶原激活物/生理学血管内皮生长因子A 血管内皮生长因子受体1 血管内皮生长因子类

来源：评论

学校读者我要写书评

暂无评论

Overexpression of VEGF 121 in immortalized endothelial cells causes conversion to slowly growing angiosarcoma and high level expression of the VEGF receptors VEGFR-1 and VEGFR-2 in vivo

引用

AMERICAN JOURNAL OF PATHOLOGY 2000年第4期156卷 1469-1476页

作者： Arbiser, JL Larsson, H Claesson-Welsh, L Bai, XH LaMontagne, K Weiss, SW Soker, S Flynn, E Brown, LF Emory Univ Sch Med Dept Dermatol Atlanta GA 30322 USA Emory Univ Sch Med Dept Pathol Atlanta GA 30322 USA Harvard Univ Sch Med Childrens Hosp Dept Surg Boston MA USA Harvard Univ Sch Med Beth Israel Deaconess Med Ctr Boston MA USA Uppsala Univ Rudbeck Lab Dept Genet & Pathol Uppsala Sweden

Vascular endothelial growth factor (VEGF or vascular permeability factor) is an important angiogenic factor that is up-regulated in numerous benign and malignant disorders, including angiosarcoma, hemangiomas, and solid tumors. To determine the functional role of VEGF in the development of endothelial tumors, we expressed primate VEGF 121 in an endothelial cell line, MS1, derived from primary murine cells by immortalization with a temperature-sensitive SV40 large T antigen. This cell line expresses the VEGFR-2 (Flk-1/Kdr) receptor for VEGF. Expression of VEGF 121 led to the development of slowly growing endothelial tumors, which were histologically well-differentiated angiosarcomas. The angiosarcomas generated from MS1 VEGF cells demonstrated up-regulation of the VEGF receptors VEGFR-2 and VEGFR-1 (Flt-1) in vivo compared with benign hemangiomas generated from MS1 cells. Treatment of these cells with the VEGFR-2 tyrosine kinase inhibitor SU 1498 led to decreased expression of ets-1, a transcription factor which has been shown to be stimulated by VEGF. These results suggest that high level expression of VEGF in endothelial cells may result in malignant transformation. This transformation process likely involves both autocrine and paracrine pathways.

关键词：细胞系转化细胞转化肿瘤内皮生长因子/代谢内皮血管/细胞学内皮血管/药物作用内皮血管/代谢内皮血管/生理学酶抑制剂/药理学血管肉瘤/病因学血管肉瘤/病理学淋巴因子/代谢小鼠裸磷酰化/药物作用灵长目原癌基因蛋白质类/代谢受体蛋白质酪氨酸激酶类/拮抗剂和抑制剂受体蛋白质酪氨酸激酶类/代谢受体生长因子/拮抗剂和抑制剂受体生长因子/代谢受体血管内皮生长因子血管内皮生长因子A 血管内皮生长因子受体1 血管内皮生长因子类动物男(雄)性小鼠

来源：评论

学校读者我要写书评

暂无评论

D114和VEGFR在氧诱导视网膜病小鼠模型中的表达及意义

引用

中山大学学报(医学科学版) 2015年第6期36卷 857-863页

作者：刘王凯苏毅华李晓瑜李易娟黄越芳余慕雪庄思齐中山大学附属第一医院儿科广东广州510080 中山大学附属第一医院眼科广东广州510080

目的:为了分析Dll4、VEGFR-1、VEGFR-2在视网膜新生血管中的表达,探讨Notch1-Dll4信号通路在氧诱导视网膜病小鼠新生血管形成中的作用。方法:选用鼠龄7d的C57BL/6J新生鼠30只,分成实验组和对照组。实验组15只,在氧浓度为(75±2)%的... 详细信息

目的:为了分析Dll4、VEGFR-1、VEGFR-2在视网膜新生血管中的表达,探讨Notch1-Dll4信号通路在氧诱导视网膜病小鼠新生血管形成中的作用。方法:选用鼠龄7d的C57BL/6J新生鼠30只,分成实验组和对照组。实验组15只,在氧浓度为(75±2)%的密闭容器中生长5d,回到室内正常空气中;对照组15只,在室内正常空气中生长。两组各取产后7d(7d post-partum,p7)、p12、p17新生鼠5只,摘除眼球,取视网膜提取RNA,以RT-PCR方法检测Dll4、VEGFR-1、VEGFR-2在视网膜中m RNA的表达。结果:RT-PCR结果显示,在p7和p12时间点时,两组间VEGFR-1表达差异无统计学意义(P>0.05);在p17时间点时,两组间VEGFR-1表达差异有统计学意义(P<0.05),实验组表达量低于对照组;VEGFR-2在各时间位点两组间表达差异无统计学意义(P>0.05);在p7时间点时,两组间Dll4表达差异无统计学意义(P>0.05);在p12和p17时间点时,两组间Dll4表达差异有统计学意义(P<0.05,P<0.05),实验组表达量低于对照组;实验组不同时间点VEGFR-1、Dll4的表达,随着时间的延长而下降(P<0.05,P<0.05);VEGFR-2的表达,随着时间的延长而升高(P<0.05);对照组不同时间点的VEGFR-2表达随着时间延长而增加(P<0.05),而VEGFR-1和Dll4的表达均不随时间变化而变化(P>0.05,P>0.05);Dll4的表达与VEGFR-1的表达呈正相关关系,相关系数r=0.905,P<0.001;而Dll4与VEGFR-2、VEGFR-1与VEGFR-2之间不存在相关关系。结论:Notch1-Dll4信号通路可能参与了VEGF调控视网膜新生血管生成的过程,Dll4在氧诱导视网膜病小鼠新生血管的形成中表达受到抑制,对VEGF未能进行有效负反馈调控;VEGFR-1的表达受到抑制,且与Dll4表达存在正相关关系;VEGFR-2可能不是视网膜新生血管形成过程中VEGF表达的主要受体。

关键词：疾病模型动物视网膜视网膜疾病统计学(主题) 新生血管化病理性血管内皮生长因子受体1 血管内皮生长因子受体2 氧动物小鼠

来源：评论

学校读者我要写书评

暂无评论

子痫前期胎盘中生长阻滞和DNA损伤45α基因及p38丝裂原活化蛋白激酶的表达

引用

中华围产医学杂志 2011年第7期14卷 396-402页

作者：刘丹丹罗欣漆洪波重庆医科大学附属第一医院妇产科 400016

目的探讨子痫前期胎盘组织中生长阻滞和DNA损伤45α（growtharrestandDNAdamage—inducible45alpha，Gadd45a）基因和p38丝裂原活化蛋白激酶（p38mitogen-activatedproteinkinase，p38MAPK）信号分子的表达，及其与血清中可溶性血管内皮生长因子受体-1（solublevascularendothelialgrowthfactorreceptor-1，sFlt-1）和可溶性endoglin（solubleendoglin，sEng）的相关性分析。方法选择2009年9月至2010年3月在重庆医科大学附属第一医院住院分娩的孕妇54例为研究对象，按病情分为子痫前期轻度组20例、子痫前期重度组16例，以足月择期剖宫产孕妇18例为对照组。采用免疫组织化学SP法检测Gadd45α及磷酸化p38MAPK（phospho—p38MAPK，P—p38MAPK）蛋白在各组胎盘组织中的定位；实时荧光定量PCR检测各组胎盘组织中Gadd45amRNA水平；Western印迹法检测各组胎盘组织中Gadd45α蛋白的表达水平、p38MAPK及p-p38MAPK的蛋白表达差异；双抗体夹心酶联免疫吸附法检测各组孕妇血清样本中sFh-1及sEng的含量，并进行单因素方差及LSD-t检验分析。结果（1）免疫组织化学检测Gadd45α与P—p38MAPK蛋白均定位于胎盘滋养层细胞胞质及胞核、血管内皮细胞胞核及少量间质细胞胞核。（2）子痫前期重度及轻度组Gadd45utuRNA相对表达水平（3．33±0．13和2．10±0．11）较正常对照组（1．01±0．18）明显上调，且子痫前期重度组高于轻度组，两两比较差异均有统计学意义（P〈O．05）。（3）Western印迹法检测正常对照组、子痫前期轻度组及重度组患者胎盘组织中Gadd45a蛋白表达水平分别为0．22±0．11、0．65±0．15、1．34±0．17；p-p38MAPK蛋白的表达水平分别为0．32士0．08、0．72±0．12、1．45±0．21，两两比较差异均有统计学意义（P〈O．05）；p38MAPK蛋白水平组间比较差异无统计学意义（P〉O．05）。（4）子痫前期轻度组、重度组孕妇血清sFlt-1、sEng水平明显高于正常对照组，且子痫前期重度组高于轻度组，两两比较差异均有统计学意义（P〈0．05）。（5）各组Gadd45α蛋白水平与孕妇血清中的sFlt-1、sEng含量呈正相关（r分别为0．88和0．87，P均〈0．05）。结论Gadd45α在子痫前期患者胎盘组织中的表达明显升高，其可能通过调控p38MAPK信号转导通路，诱使循环中的sFlt-1、sEng释放增加，从而加重胎盘血管重铸障碍和抑制滋养细胞浸润，参与子痫前期的发病。

关键词：先兆子痫核蛋白质类细胞周期蛋白质类 p38丝裂原活化蛋白激酶类血管内皮生长因子受体1 受体细胞表面抗原 CD

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：