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生长分化因子15（GDF15）缺乏通过下调Smad1/5磷酸化来阻碍人滋养层细胞侵袭，从而介导妊娠丢失。

GDF15 deficiency hinders human trophoblast invasion to mediate pregnancy loss through downregulating Smad1/5 phosphorylation.

作者信息

Zeng Yu-Ting, Liu Wen-Fang, Zheng Peng-Sheng, Li Shan

机构信息

Department of Reproductive Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of the People's Republic of China, Xi'an, Shaanxi, China.

出版信息

iScience. 2023 Sep 13;26(10):107902. doi: 10.1016/j.isci.2023.107902. eCollection 2023 Oct 20.

DOI:10.1016/j.isci.2023.107902
PMID:37766993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10520888/
Abstract

Growth differentiation factor 15 (GDF15) belongs to the Transforming growth factor β(TGF-β) superfamily. The decrease of GDF15 in the serum of pregnant women was associated with miscarriage. Both IHC and ELISA assays showed that GDF15 in trophoblast tissue and serum of pregnant women who miscarried was significantly lower than in those who had a live birth. GDF15 deficiency was associated with embryo resorption in GDF15 knockout mice through CRIPSR editing. In addition, the migration and invasion ability of HTR-8/SVneo and JEG-3 cells were promoted by GDF15. Mechanistically, GDF15 increased Smad1/5 phosphorylation, resulting in upregulating SNAI1/2, VIMENTIN and downregulating E-CADHERIN. A dual-luciferase reporter assay confirmed that Smad-binding elements (SBE) and/or GC-rich motifs were activated and target genes such as SNAI1/2, SERPINE1, and TIMP3 were transcriptionally regulated by GDF15/Smad5 signaling. Therefore, our data revealed a crucial role of GDF15 on invasion of trophoblast by upregulating the activity of TGF-β/Smad1/5 pathway.

摘要

生长分化因子15（GDF15）属于转化生长因子β（TGF-β）超家族。孕妇血清中GDF15水平降低与流产有关。免疫组化（IHC）和酶联免疫吸附测定（ELISA）均显示，流产孕妇的滋养层组织和血清中的GDF15显著低于正常分娩孕妇。通过CRISPR编辑技术发现，GDF15基因敲除小鼠中GDF15缺乏与胚胎吸收有关。此外，GDF15可促进HTR-8/SVneo和JEG-3细胞的迁移和侵袭能力。机制上，GDF15增加Smad1/5磷酸化，导致SNAI1/2、波形蛋白上调，E-钙黏蛋白下调。双荧光素酶报告基因检测证实，Smad结合元件（SBE）和/或富含GC的基序被激活，SNAI1/2、丝氨酸蛋白酶抑制剂1（SERPINE1）和金属蛋白酶组织抑制因子3（TIMP3）等靶基因受GDF15/Smad5信号通路转录调控。因此，我们的数据揭示了GDF15通过上调TGF-β/Smad1/5信号通路活性在滋养层细胞侵袭中的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/08e442412f93/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/489c2202034a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/f3b80b99fa74/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/cd06c5ca4545/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/1596675a7c2a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/cd4d7209db97/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/45d981e7eae4/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/f275f5ace605/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/08e442412f93/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/489c2202034a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/f3b80b99fa74/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/cd06c5ca4545/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/1596675a7c2a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/cd4d7209db97/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/45d981e7eae4/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/f275f5ace605/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59a/10520888/08e442412f93/gr7.jpg

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3
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Commun Biol. 2025 Mar 8;8(1):396. doi: 10.1038/s42003-025-07834-1.
4
The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.骨形态发生蛋白信号通路：在妊娠早期架起母胎串扰的桥梁。
Reprod Sci. 2025 May;32(5):1427-1445. doi: 10.1007/s43032-024-01777-4. Epub 2025 Jan 16.
5
Associations between prenatal distress, mitochondrial health, and gestational age: findings from two pregnancy studies in the USA and Turkey.产前应激、线粒体健康与孕周之间的关联：来自美国和土耳其两项妊娠研究的结果。
bioRxiv. 2025 Jan 28:2024.10.16.618719. doi: 10.1101/2024.10.16.618719.
6
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Nat Metab. 2024 Oct;6(10):1913-1921. doi: 10.1038/s42255-024-01135-3. Epub 2024 Sep 26.
7
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5
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