Positive and Negative Regulation of Angiogenesis by Soluble Vascular Endothelial Growth Factor Receptor-1.
Positive and Negative Regulation of Angiogenesis by Soluble Vascular Endothelial Growth Factor Receptor-1.
复制标题
DOI：
10.3390/ijms19051306
复制
发表时间：
2018-04-27
影响因子：
5.6
通讯作者：
Morea V
中科院分区：
文献类型：
--
作者：
Failla CM;Carbo M;Morea V
血管内皮生长因子受体（VEGFR）-1以不同形式存在，来源于同一基因的选择性剪接。除了跨膜形式，内皮细胞产生可溶性VEGFR-1（sVEGFR-1）同种型，而非内皮细胞产生sVEGFR-1和不同的可溶性分子，称为可溶性fms样酪氨酸激酶（sFlt）1-14。通过结合血管内皮生长因子（VEGF）家族的成员，可溶形式减少可用于与其跨膜受体相互作用的VEGF的量，从而负调节VEGF介导的信号传导。与这种活性一致，高水平的循环sVEGFR-1或sFlt 1 -14与涉及血管功能障碍的不同病理状况相关。此外，sVEGFR-1和sFlt 1 -14在血管生成中具有额外的作用：它们沉积在内皮细胞和周细胞细胞外基质中，并与细胞膜组分相互作用。内皮细胞膜上sVEGFR-1与α5β1整联蛋白的相互作用调节血管生长，触发动态促血管生成表型。sVEGFR-1/sFlt 1 -14与脂筏中细胞膜鞘糖脂的相互作用控制肾细胞形态和肾小球屏障功能。这些细胞-基质接触代表了药物干预的有吸引力的新靶点，除了那些解决VEGF及其受体之间的相互作用。
Vascular endothelial growth factor receptor (VEGFR)-1 exists in different forms, derived from alternative splicing of the same gene. In addition to the transmembrane form, endothelial cells produce a soluble VEGFR-1 (sVEGFR-1) isoform, whereas non-endothelial cells produce both sVEGFR-1 and a different soluble molecule, known as soluble fms-like tyrosine kinase (sFlt)1-14. By binding members of the vascular endothelial growth factor (VEGF) family, the soluble forms reduce the amounts of VEGFs available for the interaction with their transmembrane receptors, thereby negatively regulating VEGFR-mediated signaling. In agreement with this activity, high levels of circulating sVEGFR-1 or sFlt1-14 are associated with different pathological conditions involving vascular dysfunction. Moreover, sVEGFR-1 and sFlt1-14 have an additional role in angiogenesis: they are deposited in the endothelial cell and pericyte extracellular matrix, and interact with cell membrane components. Interaction of sVEGFR-1 with α5β1 integrin on endothelial cell membranes regulates vessel growth, triggering a dynamic, pro-angiogenic phenotype. Interaction of sVEGFR-1/sFlt1-14 with cell membrane glycosphingolipids in lipid rafts controls kidney cell morphology and glomerular barrier functions. These cell–matrix contacts represent attractive novel targets for pharmacological intervention in addition to those addressing interactions between VEGFs and their receptors.
登录
查看更多内容
影响因子：
158.5
作者：
Eremina, Vera;Jefferson, J. Ashley;Quaggin, Susan E.
通讯作者：
Quaggin, Susan E.
影响因子：
16.6
作者：
Cudmore, Melissa J.;Hewett, Peter W.;Ahmed, Asif
通讯作者：
Ahmed, Asif
影响因子：
5.6
作者：
Dumnicka P;Kuśnierz-Cabala B;Sporek M;Mazur-Laskowska M;Gil K;Kuźniewski M;Ceranowicz P;Warzecha Z;Dembiński A;Bonior J;Drożdż R
通讯作者：
Drożdż R
影响因子：
5.4
作者：
Dewerchin, Mieke;Carmeliet, Peter
通讯作者：
Carmeliet, Peter
影响因子：
3.7
作者：
Amraoui F;Spijkers L;Hassani Lahsinoui H;Vogt L;van der Post J;Peters S;Afink G;Ris-Stalpers C;van den Born BJ
通讯作者：
van den Born BJ