Targeting colony stimulating factor-1 receptor signalling to treat ectopic pregnancy.
Targeting colony stimulating factor-1 receptor signalling to treat ectopic pregnancy.
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DOI：
10.1038/s41598-020-72785-y
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发表时间：
2020-09-24
影响因子：
4.6
通讯作者：
Horne AW
中科院分区：
文献类型：
--
作者：
Ahmad SF;Duncan WC;Campbell LL;Beaty RE;Koscielniak M;Collins F;Saunders PTK;Horne AW
1-2%的妊娠是异位妊娠，大多数植入输卵管。甲氨蝶呤是一种dna合成（S相）抑制剂，自1991年以来一直用于稳定EP妇女的门诊治疗。然而，甲氨蝶呤的临床和成本效益有限，仅在这些妇女中使用25-30%。对EP的更好的医学治疗的需求尚未得到满足。集落刺激因子-1 （CSF-1）促进胎盘形成并创造促炎环境，这是维持正常妊娠的基础。我们假设CSF-1也参与了EP的形成和维持。在此，我们证明了在永生化的妊娠早期滋养细胞中，CSF-1受体（CSF-1R）及其配体（CSF-1）的免疫定位。我们发现一种特异性的CSF-1R激酶抑制剂GW2580可以消除CSF-1诱导的滋养细胞增殖和迁移，并且可能具有细胞毒性。然后，我们证实了CSF-1R和CSF-1在EP患者异位着床部位的细胞滋养细胞和合胞滋养细胞中的表达。我们的数据表明，CSF-1参与了EP中滋养细胞的存活和增殖。这表明，CSF-1/CSF-1R信号轴的药理破坏可能是一种新的EP治疗方法的基础。
1–2% of pregnancies are ectopic, the majority implanting in the Fallopian tube. A single, systemic dose of methotrexate, a DNA-synthesis (S phase) inhibitor, has been used since 1991 for outpatient treatment of women with stable EP. However, methotrexate has limited clinical and cost effectiveness, restricting its use to 25–30% of these women. There is an unmet need for better medical treatment for EP. Colony stimulating factor-1 (CSF-1) promotes placentation and creates a pro-inflammatory environment that is fundamental for the maintenance of a normal pregnancy. We hypothesised that CSF-1 is also involved in the placentation and maintenance of an EP. Herein, we demonstrate the immunolocalisation of the CSF-1 receptor (CSF-1R) as well as its ligand (CSF-1) in immortalised first trimester trophoblast cells. We show that a specific CSF-1R kinase inhibitor, GW2580, abolishes CSF-1 induced trophoblast cell proliferation and migration and can be cytotoxic. We then demonstrate the expression of CSF-1R and CSF-1 in the cytotrophoblast and syncytiotrophoblast within ectopic implantation sites from women with EP. Our data suggests that CSF-1 is involved in the survival and proliferation of trophoblast cells in EP. This suggests that pharmacological disruption of CSF-1/CSF-1R signaling axis could be the basis of a new therapeutic for EP.
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影响因子：
11.2
作者：
Moughon DL;He H;Schokrpur S;Jiang ZK;Yaqoob M;David J;Lin C;Iruela-Arispe ML;Dorigo O;Wu L
通讯作者：
Wu L
DOI：
10.1093/humrep/dep438
发表时间：
2010-03
期刊：
Human reproduction (Oxford, England)
影响因子：
--
作者：
Shao R
通讯作者：
Shao R
影响因子：
20.3
作者：
Edwards, David K., V;Watanabe-Smith, Kevin;Tyner, Jeffrey W.
通讯作者：
Tyner, Jeffrey W.
影响因子：
7.2
作者：
Nilsson, Ulrika W.;Johns, Terrance G.;Tong, Stephen
通讯作者：
Tong, Stephen
影响因子：
6.7
作者：
Peng, Bo;Klausen, Christian;Bedaiwy, Mohamed A.
通讯作者：
Bedaiwy, Mohamed A.