Serum response factor is required for sprouting angiogenesis and vascular integrity
Serum response factor is required for sprouting angiogenesis and vascular integrity
复制标题
DOI：
10.1016/j.devcel.2008.07.019
复制
发表时间：
2008-09-16
影响因子：
11.8
通讯作者：
Li, Zhenlin
中科院分区：
文献类型：
--
作者：
Franco, Claudio Areias;Mericskay, Mathias;Li, Zhenlin
血清反应因子(SRF)是一种转录因子，控制细胞骨架蛋白和即刻早期基因在不同细胞类型中的表达。在这里，我们发现SRF的表达仅限于小鼠胚胎中毛细血管等小血管的内皮细胞。EC特异性SRF缺失导致小鼠发育11.5天(E11.5天)出现动脉瘤和出血，E14.5天死亡。突变胚胎表现出毛细血管密度降低和EC迁移缺陷，顶端细胞和内皮细胞中丝状足的数量较少，显示出肌动蛋白聚合和细胞间连接的缺陷。我们发现SRF对于体内和体外内皮细胞中VE-钙粘蛋白和β-肌动蛋白的表达是必不可少的。此外，敲除内皮细胞中的SRF会削弱血管内皮生长因子和成纤维细胞生长因子诱导的体外血管生成。综上所述，我们的结果表明，SRF在小鼠胚胎的萌发血管生成和小血管完整性方面发挥着重要作用。
Serum response factor (SRF) is a transcription factor that controls the expression of cytoskeletal proteins and immediate early genes in different cell types. Here, we found that SRF expression is restricted to endothelial cells (ECs) of small vessels such as capillaries in the mouse embryo. EC-specific Srf deletion led to aneurysms and hemorrhages from 11.5 days of mouse development (E11.5) and lethality at E14.5. Mutant embryos presented a reduced capillary density and defects in EC migration, with fewer numbers of filopodia in tip cells and ECs showing defects in actin polymerization and intercellular junctions. We show that SRF is essential for the expression of VE-cadherin and beta-actin in ECs both in vivo and in vitro. Moreover, knockdown of SRF in ECs impaired VEGF- and FGF-induced in vitro angiogenesis. Taken together, our results demonstrate that SRF plays an important role in sprouting angiogenesis and small vessel integrity in the mouse embryo.