Abraham Sunil, Sanjay Geetha, Majiyd Noushin Abdul, Chinnaiah Amutha
Department of Animal Behavior & Physiology, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, India.
Innov4Sight Health and Biomedical Systems Pvt. Ltd. Biologics Lab- # EGF11, Bangalore Bioinnovation Centre, Bangalore Helix Biotech Park, Electronics City Phase 1, Bangalore, Karnataka, 560100, India.
J Genet Eng Biotechnol. 2021 Feb 1;19(1):23. doi: 10.1186/s43141-021-00118-1.
In this study, Vascular Endothelial Growth Factor 121 expressed abundantly in endometrial stromal cells is encapsulated with poly-l-lactide and characterized the properties for endometrial angiogenesis. We studied the migration, proliferation and the protein levels of human immortalized endometrium stromal cells after treating the cells with recombinant Vascular Endothelial Growth Factor (200 and 500 nanogram), and poly-l-lactide loaded Vascular Endothelial Growth Factor 121 (day 1, 20 and 30). The present study explains endometrium angiogenesis because endometrium plays an important role in pregnancy.
Migration and proliferation studies in endometrium cells proved the efficiency of Vascular Endothelial Growth Factor and poly-l-lactide loaded Vascular Endothelial Growth Factor 121. This proliferated and increased the migration of the cells in vitro and also activated the Protein kinase B, Phosphatidylinositol-4, 5-Bisphosphate 3-Kinase Catalytic Subunit Beta, α-Smooth muscle actin and vascular endothelial growth factor receptor 2 pathways. Western blot analysis showed the increased expression levels of kinases, smooth muscle actin and vascular endothelial growth factor receptor 2 after the treatment with Vascular Endothelial Growth Factor and poly-l-lactide loaded Vascular Endothelial Growth Factor 121 particles in comparison to the control group. The elevated levels of α-Smooth muscle actin in endometrium cells with Vascular Endothelial Growth Factor prove the regulation of angiogenesis in vitro.
Endometrium thickness is one of the important factors during implantation of embryo and pregnancy. Slow release of VEGF from PLA encapsulated microparticle further controls the endothelial cell proliferation and migration and helps in the promotion of angiogenesis. The combined effect studied in vitro could be used as a pro-angiogenic drug on further in vivo confirmation.
在本研究中，在子宫内膜基质细胞中大量表达的血管内皮生长因子121被聚左旋乳酸包裹，并对其促进子宫内膜血管生成的特性进行了表征。我们在用重组血管内皮生长因子（200和500纳克）以及负载血管内皮生长因子121的聚左旋乳酸（第1天、第20天和第30天）处理人永生化子宫内膜基质细胞后，研究了这些细胞的迁移、增殖以及蛋白水平。本研究解释了子宫内膜血管生成，因为子宫内膜在妊娠中起着重要作用。
对子宫内膜细胞的迁移和增殖研究证明了血管内皮生长因子以及负载血管内皮生长因子121的聚左旋乳酸的有效性。这在体外促进了细胞增殖并增加了细胞迁移，还激活了蛋白激酶B、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基β、α-平滑肌肌动蛋白和血管内皮生长因子受体2信号通路。蛋白质印迹分析表明，与对照组相比，在用血管内皮生长因子和负载血管内皮生长因子121的聚左旋乳酸颗粒处理后，激酶、平滑肌肌动蛋白和血管内皮生长因子受体2的表达水平升高。血管内皮生长因子处理的子宫内膜细胞中α-平滑肌肌动蛋白水平升高证明了体外血管生成的调控。
子宫内膜厚度是胚胎着床和妊娠期间的重要因素之一。从聚乳酸包裹的微粒中缓慢释放血管内皮生长因子进一步控制内皮细胞的增殖和迁移，并有助于促进血管生成。体外研究的联合作用在进一步的体内验证后可作为一种促血管生成药物。
