FGA Controls VEGFA Secretion to Promote Angiogenesis by Activating the VEGFR2-FAK Signalling Pathway.
FGA Controls VEGFA Secretion to Promote Angiogenesis by Activating the VEGFR2-FAK Signalling Pathway.
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DOI：
10.3389/fendo.2022.791860
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发表时间：
2022
影响因子：
5.2
通讯作者：
Chang, Xiaohong
中科院分区：
文献类型：
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作者：
Li, Hui;Cai, E.;Cheng, Hongyan;Ye, Xue;Ma, Ruiqiong;Zhu, Honglan;Chang, Xiaohong
我们的前期工作发现纤维蛋白原α链（FGA）在子宫内膜异位症（EM）患者中高表达，并能促进子宫内膜间质细胞的迁移和侵袭。血管生成是EM发生发展的关键条件。本研究的目的是阐明FGA在子宫内膜间质细胞参与EM血管生成中的作用。采用免疫组化法检测EM与非EM在位内膜中微血管密度（MVD）和VEGF的表达。收集人原代在位子宫内膜基质细胞（EuESC）和FGA敲低的永生化子宫内膜基质细胞系hEM 15 A的条件培养基（CM），并用于处理人脐静脉内皮细胞（HUVECs）。采用试管形成实验、EdU实验、创伤实验、transwell实验和流式细胞术等方法检测HUEVC的功能。HUVECs的血管生成能力进一步使用基质胶塞测定与BALB/c裸鼠体内。免疫荧光法检测F-actin和VE-cadherin的表达。采用RT-PCR和Western blotting检测子宫内膜间质细胞血管生成相关因子的表达及HUVECs下游信号通路的变化。EM患者在位内膜中MVD和VEGF表达均显著高于非EM患者正常内膜，EM患者MVD增高提示复发风险增高。在功能上，我们发现，CM与FGA敲低子宫内膜基质细胞可以抑制HUVECs的迁移和管形成在体外和体内，而没有显着的影响HUVECs的增殖，凋亡和细胞周期。机械地，在FGA敲低的hEM 15 A细胞中，VEGFA、PDGF、FGF-B、VEGF、MMP-2和MMP-9的表达降低。CM的hEM 15 A细胞与FGA敲低减少微丝和伪足的数量，以及VE-钙粘蛋白的表达，并抑制VEGFR 2的活性和FAK信号通路在HUVECs。我们的研究表明，FGA可以通过潜在的VEGA-VEGFR-FAK信号轴增强子宫内膜基质细胞与HUVECs之间的相互作用，并促进EM血管生成，揭示了一种有希望的治疗EM的方法。
Our previous work revealed the high expression of fibrinogen alpha chain (FGA) in patients with endometriosis (EM) and that it could promote the migration and invasion of endometrial stromal cells. Angiogenesis is the key condition for the development of EM. This study was aimed to elucidate the role of FGA in endometrial stromal cells involved in angiogenesis in EM. Immunohistochemistry was used to detect the microvessel density (MVD) and VEGF expression in the eutopic endometrium samples from EM and non-EM. The conditioned medium (CM) of human primary eutopic endometrial stromal cells (EuESC) and immortalized endometrial stromal cell line hEM15A with FGA knockdown were collected and used to treat human umbilical vein endothelial cells (HUVECs). Then, tube formation assay, EdU assay, wound assay, transwell assay and flow cytometry assays were performed to assess the function of HUEVCs in vitro. The angiogenic capability of HUVECs was further measured using a matrigel plug assay with BALB/c nude mice in vivo. Immunofluorescence was used to detect the expression of F-actin and VE-cadherin. RT-PCR and western blotting were used to detect the expression of angiogenesis-related factors in endometrial stromal cells and downstream signalling pathways in HUVECs. MVD and VEGF expression in the eutopic endometrium of EM patients were significantly higher than those in the normal endometrium of non-EM patients, and the increased MVD in EM indicates an increased risk of recurrence. Functionally, we found that CM of endometrial stromal cells with FGA knockdown could inhibit HUEVCs migration and tube formation in vitro and in vivo, while having no significant effect on HUVECs proliferation, apoptosis and cell cycle. Mechanically, the expression of VEGFA, PDGF, FGF-B, VEGF, MMP-2 and MMP-9 was reduced in hEM15A cells with FGA knockdown. CM of hEM15A cells with FGA knockdown reduced the number of microfilaments and pseudopodia, as well as the expression of VE-cadherin, and inhibited the activity of VEGFR2 and the FAK signalling pathway in HUVECs. Our study demonstrated FGA could enhance the interaction between endometrial stromal cells and HUVECs via the potential VEGA-VEGFR-FAK signalling axis and promote EM angiogenesis, revealing a promising therapeutic approach for EM.
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DOI：
10.12659/msm.881707
发表时间：
2011-04
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Liu H;Lang JH
通讯作者：
Lang JH
影响因子：
3.4
作者：
Duan S;Gong B;Wang P;Huang H;Luo L;Liu F
通讯作者：
Liu F
影响因子：
5.6
作者：
Mongiat M;Andreuzzi E;Tarticchio G;Paulitti A
通讯作者：
Paulitti A
影响因子：
9.8
作者：
Protopsaltis, Nicholas J.;Liang, Wei;Ferrara, Napoleone
通讯作者：
Ferrara, Napoleone
DOI：
10.1038/nrd2792
发表时间：
2009-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
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