PD-L1 enhances migration and invasion of trophoblasts by upregulating ARHGDIB via transcription factor PU.1.
PD-L1 enhances migration and invasion of trophoblasts by upregulating ARHGDIB via transcription factor PU.1.
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DOI：
10.1038/s41420-022-01171-6
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发表时间：
2022-09-22
影响因子：
7
通讯作者：
Wang, Kai
中科院分区：
文献类型：
--
作者：
Zhang, Ruonan;Jia, Linyan;Meng, Lulu;Peng, Hao;Zhang, Donghai;He, Qizhi;Duan, Tao;Wang, Kai
作为人胎盘的主要组成细胞，滋养层细胞通过一系列过程增殖、分化并侵入子宫内膜，这些过程受到激素、细胞因子和生长因子介导的细胞间信号的精确调控。程序性死亡配体1（PD - L1）是免疫检查点抑制剂反应的生物标志物，在妊娠进展过程中可调节母胎免疫耐受。最近发现，PD - L1可能通过影响滋养层细胞的功能来调控产科并发症。因此，我们检测了PD - L1在人胎盘中的表达和定位，并在滋养层细胞系HTR - 8/SVneo和绒毛外植体培养模型中观察了PD - L1对滋养层细胞迁移和侵袭的影响。最后，我们通过RNA测序和生物信息学分析探究了PD - L1调控滋养层细胞迁移和侵袭的分子机制。我们的数据显示，PD - L1主要在合体滋养层细胞中表达，且其蛋白水平随孕周增加而升高。有趣的是，与正常胎盘相比，子痫前期患者胎盘组织中PD - L1的蛋白表达显著降低。重要的是，在HTR - 8/SVneo细胞和绒毛外植体培养模型中，敲低或过表达PD - L1后，滋养层细胞的迁移和侵袭能力发生了显著变化，这部分是通过转录因子PU.1（由Spi1编码）调控Rho GDP解离抑制因子β（ARHGDIB）的表达来介导的。这些结果表明，PD - L1高度参与滋养层细胞迁移和侵袭的调控，为胎盘源性妊娠疾病的诊断和治疗提供了一个潜在靶点。
As the main constituent cells of the human placenta, trophoblasts proliferate, differentiate, and invade the uterine endometrium via a series of processes, which are regulated exquisitely through intercellular signaling mediated by hormones, cytokines, and growth factors. Programmed cell death ligand 1 (PD-L1) is a biomarker of the response to immune checkpoint inhibitors and can regulate maternal-fetal immune tolerance during pregnancy progression. Recently, it was found that PD-L1 may regulate obstetric complications by affecting the function of trophoblasts. Therefore, we examined the expression and localization of PD-L1 in the human placenta and observed the effects of PD-L1 on trophoblasts migration and invasion in both the trophoblasts line HTR-8/SVneo and an extravillous explant culture model. Finally, we explored the molecular mechanisms underlying PD-L1-regulated trophoblasts migration and invasion through RNA sequencing and bioinformatics analysis. Our data showed that PD-L1 was mainly expressed in syncytiotrophoblasts and that its protein levels increased with gestational age. Interestingly, the protein expression of PD-L1 was significantly decreased in placentas from pregnancies with preeclampsia compared with normal placentas. Importantly, the migration and invasion abilities of trophoblasts were significantly changed after knockdown or overexpression of PD-L1 in HTR-8/SVneo cells and an extravillous explant culture model, which was partially mediated through the transcription factor PU.1 (encoded by Spi1)-regulated Rho GDP-dissociation inhibitor beta (ARHGDIB) expression. These results suggested that PD-L1 was highly involved in the regulation of trophoblasts migration and invasion, providing a potential target for the diagnosis and treatment of placenta-derived pregnancy disorders.
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影响因子：
4.8
作者：
Gao, Jun;Dai, Chao;Zhou, Fan
通讯作者：
Zhou, Fan
影响因子：
5.7
作者：
Lu S;Sun Z;Hu W;Yin S;Zhao C;Hu H
通讯作者：
Hu H
影响因子：
3.1
作者：
Meggyes, Matyas;Miko, Eva;Szereday, Laszlo
通讯作者：
Szereday, Laszlo
DOI：
10.1016/bs.apha.2017.08.002
发表时间：
2018
期刊：
Advances in pharmacology (San Diego, Calif.)
影响因子：
--
作者：
Wang X;Khalil RA
通讯作者：
Khalil RA
影响因子：
3.3
作者：
Lu, Bingjian;Teng, Xiaodong;Lu, Yan
通讯作者：
Lu, Yan