Complement 5a-mediated trophoblasts dysfunction is involved in the development of pre-eclampsia.
Complement 5a-mediated trophoblasts dysfunction is involved in the development of pre-eclampsia.
复制标题
补体 5a 介导的滋养层功能障碍与先兆子痫的发生有关。
DOI：
10.1111/jcmm.13466
复制
发表时间：
2018-03
影响因子：
5.3
通讯作者：
Gao PJ
中科院分区：
文献类型：
--
作者：
Ma Y;Kong LR;Ge Q;Lu YY;Hong MN;Zhang Y;Ruan CC;Gao PJ
先兆子痫（PE）是一种危及生命的多系统疾病，可导致孕产妇和新生儿死亡和发病。新出现的证据表明，补体系统的激活与PE的病理过程有关。然而，人们对PE发生过程中补体激活的详细细胞和分子机制知之甚少。在这项研究中，我们报道了补体5a（C5 a）在异常胎盘形成中起关键作用，这是PE发病所必需的。我们检测到先兆子痫胎盘的巨噬细胞中C5 a沉积和滋养层中C5 a受体（C5 aR）表达升高。进一步的研究表明，C5 a通过介导血管生成因子（如可溶性fms样酪氨酸激酶1（sFlt 1）和胎盘生长因子（PlGF））的失衡，刺激滋养层细胞朝向抗血管生成表型。此外，C5 a抑制滋养层细胞的迁移和管形成，而用siRNA敲低C5 aR拯救了迁移和管形成能力。我们还发现，母亲C5 a血清水平在PE的妇女增加，并与母亲的血压和动脉僵硬度呈正相关。这些结果表明，胎盘C5 a/C5 aR通路通过调节胎盘滋养细胞功能障碍而促进了PE的发生，表明C5 a可能是该疾病的新的治疗可能性。
Pre‐eclampsia (PE) is a life‐threatening multisystem disorder leading to maternal and neonatal mortality and morbidity. Emerging evidence showed that activation of the complement system is implicated in the pathological processes of PE. However, little is known about the detailed cellular and molecular mechanism of complement activation in the development of PE. In this study, we reported that complement 5a (C5a) plays a pivotal role in aberrant placentation, which is essential for the onset of PE. We detected an elevated C5a deposition in macrophages and C5a receptor (C5aR) expression in trophoblasts of pre‐eclamptic placentas. Further study showed that C5a stimulated trophoblasts towards an anti‐angiogenic phenotype by mediating the imbalance of angiogenic factors such as soluble fms‐like tyrosine kinase 1 (sFlt1) and placental growth factor (PIGF). Additionally, C5a inhibited the migration and tube formation of trophoblasts, while, C5aR knockdown with siRNA rescued migration and tube formation abilities. We also found that maternal C5a serum level was increased in women with PE and was positively correlated with maternal blood pressure and arterial stiffness. These results demonstrated that the placental C5a/C5aR pathway contributed to the development of PE by regulating placental trophoblasts dysfunctions, suggesting that C5a may be a novel therapeutic possibility for the disease.
登录
查看更多内容
影响因子：
3.8
作者：
Lynch, A. M.;Salmon, J. E.
通讯作者：
Salmon, J. E.
影响因子：
3.4
作者：
Denny, Kerina J.;Coulthard, Liam G.;Woodruff, Trent M.
通讯作者：
Woodruff, Trent M.
影响因子：
9.8
作者：
Oyama-Kato, Mizuho;Ohmichi, Masahide;Kurachi, Hirohisa
通讯作者：
Kurachi, Hirohisa
影响因子：
7.3
作者：
Lokki AI;Heikkinen-Eloranta J;Jarva H;Saisto T;Lokki ML;Laivuori H;Meri S
通讯作者：
Meri S
影响因子：
8.3
作者：
Macedo, Maria L.;Luminoso, Daniele;Nicolaides, Kypros H.
通讯作者：
Nicolaides, Kypros H.