胎盘生长因子转基因小鼠中血管生成缺陷导致的妊娠丢失和生长受限
Gestational loss and growth restriction by angiogenic defects in placental growth factor transgenic mice.
作者信息
Kang Min-Cheol, Park Seo Jin, Kim Hei Jung, Lee Jinhee, Yu Dong Hoon, Bae Ki Beom, Ji Young Rae, Park Si Jun, Jeong Jain, Jang Woo Young, Kim Jung-Hak, Choi Myung-Sook, Lee Dong-Seok, Lee Hyun-Shik, Lee Sanggyu, Kim Sung Hyun, Kim Myoung Ok, Park Gyeongsin, Choo Yeon Sik, Cho Je-Yoel, Ryoo Zae Young
机构信息
From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
出版信息
Arterioscler Thromb Vasc Biol. 2014 Oct;34(10):2276-82. doi: 10.1161/ATVBAHA.114.303693. Epub 2014 Aug 21.
OBJECTIVE
Angiogenesis is an important biological process during development, reproduction, and in immune responses. Placental growth factor (PlGF) is a member of vascular endothelial growth factor that is critical for angiogenesis and vasculogenesis. We generated transgenic mice overexpressing PlGF in specifically T cells using the human CD2-promoter to investigate the effects of PlGF overexpression.
APPROACH AND RESULTS
Transgenic mice were difficult to obtain owing to high lethality; for this reason, we investigated why gestational loss occurred in these transgenic mice. Here, we report that placenta detachment and inhibition of angiogenesis occurred in PlGF transgenic mice during the gestational period. Moreover, even when transgenic mice were born, their growth was restricted.
CONCLUSIONS
Conclusively, PlGF overexpression prevents angiogenesis by inhibiting Braf, extracellular signal-regulated kinase activation, and downregulation of HIF-1α in the mouse placenta. Furthermore, it affected regulatory T cells, which are important for maintenance of pregnancy.
目的
血管生成是发育、生殖及免疫反应过程中的一个重要生物学过程。胎盘生长因子（PlGF）是血管内皮生长因子家族的一员，对血管生成和血管发生至关重要。我们利用人CD2启动子构建了在特定T细胞中过表达PlGF的转基因小鼠，以研究PlGF过表达的影响。
方法与结果
由于高致死率，难以获得转基因小鼠；因此，我们研究了这些转基因小鼠发生妊娠丢失的原因。在此，我们报告在妊娠期PlGF转基因小鼠中发生了胎盘剥离和血管生成抑制。此外，即使转基因小鼠出生后，其生长也受到限制。
结论
总之，PlGF过表达通过抑制小鼠胎盘中的Braf、细胞外信号调节激酶激活及HIF-1α下调来阻止血管生成。此外，它还影响了对维持妊娠很重要的调节性T细胞。
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