Hypoxia and extracellular matrix proteins influence angiogenesis and lymphangiogenesis in mouse embryoid bodies.
Hypoxia and extracellular matrix proteins influence angiogenesis and lymphangiogenesis in mouse embryoid bodies.
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DOI：
10.3389/fphys.2011.00103
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发表时间：
2011
影响因子：
4
通讯作者：
Muthuchamy M
中科院分区：
文献类型：
--
作者：
Foskett AM;Ezekiel UR;Trzeciakowski JP;Zawieja DC;Muthuchamy M
与淋巴管生成相比，血管生成的调节机制相对成熟。很少有研究表明，血管内皮生长因子VEGF-A/C与低氧或胶原基质相结合，可以促进小鼠类胚体(EB)的淋巴管结构和血管发育。在这项研究中，我们验证了这样的假设，即低氧和延长的VEGF-A/C处理除了诱导血管生成外，还可以诱导小鼠EBS早期淋巴管生成，在类似的条件下，特定的细胞外基质(ECM)蛋白将促进淋巴管样结构而不是血管生成。将EBS置于四种条件下，分别在常氧和低氧(分别为21%和2.6%O2)条件下，加或不加VEGF-A/C。对常氧和低氧EBS进行基因芯片分析，免疫荧光数据显示早期淋巴管内皮细胞(LEC)标志物、淋巴管内皮透明质酸受体1(LYVE1)和繁荣相关同源盒1(Prox1)在早期表达很低。MECA-32和Prox1/LYVE1的双重免疫荧光显示，低氧和VEGF-A/C联合处理促进了血管样结构的形成，而在E22.5的EBS中仅检测到Prox1+/LYVE1+LECs。此外，EBS生长在层粘连蛋白或I型胶原涂层平板上，并接受如上所述的四种处理。结果表明，与层粘连蛋白上生长的EBS相比，E36.5的EBS中的LECs与I型胶原附着得更好，形成了一个有组织的淋巴管样结构网络。然而，在同样的条件下，血管样结构不那么受欢迎。总而言之，我们的数据表明，低氧与生长因子联合促进血管生成，而这些条件与特定的ECM蛋白相结合有利于小鼠EBS的淋巴管生成过程。
Regulatory mechanisms for angiogenesis are relatively well established compared to lymphangiogenesis. Few studies have shown that a combination of vascular endothelial growth factor VEGF-A/C with hypoxia or collagen matrix promotes lymphatic structures along with blood vessel development in mouse embryoid bodies (EB). In this study we tested the hypothesis that while hypoxia combined with prolonged VEGF-A/C treatment would induce early lymphangiogenesis in addition to angiogenesis in mouse EBs, under similar conditions specific extracellular matrix (ECM) proteins would promote lymphatic vessel-like structures over angiogenesis. EBs were subjected to four conditions and were maintained under normoxia and hypoxia (21% and 2.6% O2, respectively) with or without VEGF-A/C. Microarray analyses of normoxic and hypoxic EBs, and immunofluorescence data showed very low expression of early lymphatic endothelial cell (LEC) markers, lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), and prospero-related homeobox 1 (Prox1) at early time points. Double immunofluorescence using MECA-32 and Prox1/LYVE1 demonstrated that combined hypoxia and VEGF-A/C treatment promoted formation of blood vessel-like structures, whereas only Prox1+/LYVE1+ LECs were detected in EBs at E22.5. Furthermore, EBs were grown on laminin or collagen-I coated plates and were subjected to the four treatments as described above. Results revealed that LECs in EBs at E36.5 attached better to collagen-I, resulting in an organized network of lymphatic vessel-like structures as compared to EBs grown on laminin. However, blood vessel-like structures were less favored under these same conditions. Collectively, our data demonstrate that hypoxia combined with growth factors promotes angiogenesis, whereas combination of these conditions with specific ECM proteins favors lymphangiogenesis processes in mouse EBs.
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影响因子：
11.8
作者：
Gale, NW;Thurston, G;Yancopoulos, GD
通讯作者：
Yancopoulos, GD
影响因子：
2.7
作者：
Ezekiel, Uthayashanker R;Muthuchamy, Mariappan;Heuertz, Rita M
通讯作者：
Heuertz, Rita M
影响因子：
7.8
作者：
Banerji, S;Ni, J;Wang, S X;Clasper, S;Su, J;Tammi, R;Jones, M;Jackson, D G
通讯作者：
Jackson, D G
DOI：
10.1161/01.atv.0000217610.58032.b7
发表时间：
2006-05-01
影响因子：
8.7
作者：
Kreuger, J;Nilsson, I;Claesson-Welsh, L
通讯作者：
Claesson-Welsh, L
影响因子：
56.9
作者：
Dumont, DJ;Jussila, L;Alitalo, K
通讯作者：
Alitalo, K