Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts.
Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts.
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胶原I通过抑制滋养细胞的增殖和侵袭诱导子痫前期样症状。
DOI：
10.3389/fendo.2021.664766
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发表时间：
2021
影响因子：
5.2
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Feng Y;Chen X;Wang H;Chen X;Lan Z;Li P;Cao Y;Liu M;Lv J;Chen Y;Wang Y;Sheng C;Huang Y;Zhong M;Wang Z;Yue X;Huang L
子痫前期是一种常见的产科疾病，影响全世界2-8%的妊娠。纤维化是子痫前期胎盘发生的重要组织学变化，可能与I型胶原的过量沉积有关。然而，纤维化胎盘和I型胶原在子痫前期发病中的作用尚不清楚。因此，我们采用Masson染色、Sirius红染色和western blotting分析人胎盘中胶原沉积和I型胶原的表达。进一步，我们在C57BL/6小鼠中研究了I型胶原蛋白在子痫前期发病中的作用。利用HTR-8/SVneo细胞通过转录组测序和药物激动剂研究I型胶原在滋养细胞中的作用机制。人子痫前期胎盘的干绒毛和终绒毛纤维化程度明显高于正常胎盘，并以I型胶原沉积为特征。在体内，妊娠第0.5天单次注射I型胶原可导致妊娠第4.5 ~ 17.5天妊娠小鼠收缩压升高，体重和胚胎数量减少，胎盘I型胶原表达和纤维化程度较对照小鼠增强。在体外实验中，I型胶原可抑制HTR-8SV/neo细胞的增殖和侵袭。这种作用可以通过ERK和β-连环蛋白激动剂治疗逆转。此外，转录组测序显示，HTR-8SV/neo细胞中与细胞增殖和侵袭相关的信号通路显著下调。因此，我们提出胶原I通过抑制ERK磷酸化和WNT/β-catenin信号通路抑制滋养层细胞的增殖和侵袭，从而诱导子痫前期样症状。我们的发现可能为发现用于子痫前期治疗的小分子抑制剂铺平道路，未来需要更大样本量的研究。
Preeclampsia is a common obstetric disorder affecting 2-8% of pregnancy worldwide. Fibrosis is an important histological change occurring in preeclamptic placenta, and might depend on the excess deposition of collagen I. However, the role of fibrotic placenta and collagen I in the pathogenesis of preeclampsia remains unclear. Therefore, we analyzed the collagen deposition and the expression of Collagen I in human placenta by Masson staining, Sirius red staining and western blotting. Further, the role of collagen I in preeclampsia pathogenesis was studied in C57BL/6 mice. HTR-8/SVneo cells were used to investigate the mechanisms underlying the effects of collagen I in trophoblasts by transcriptome sequencing and pharmacological agonists. Human preeclamptic placenta exhibited a significantly higher degree of fibrosis in stem villi and terminal villi than normal placenta, and was characterized by collagen I deposition. In vivo, a single injection of collagen I on gestational day 0.5 led to an increase in systolic pressure of pregnant mice from gestational days 4.5–17.5, to a decrease in weight and number of embryos, and to enhanced placental collagen I expression and degree of fibrosis compared with control mice. In vitro, collagen I attenuated the proliferation and invasion of HTR-8SV/neo cells. This effect could be reversed by treatment with agonists of ERK and β-catenin. Moreover, transcriptome sequencing demonstrated that signaling pathways related to cell proliferation and invasion were significantly downregulated in HTR-8SV/neo cells. Thus, we propose that collagen I induced preeclampsia-like symptoms by suppressing the proliferation and invasion of trophoblasts through inhibition of the ERK phosphorylation and WNT/β-catenin signaling pathways. Our findings could pave the way to the discovery of small-molecule inhibitors for preeclampsia treatment and future studies with larger sample size are required.
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影响因子：
4.6
作者：
Kaartokallio T;Cervera A;Kyllönen A;Laivuori K;Kere J;Laivuori H;FINNPEC Core Investigator Group
通讯作者：
FINNPEC Core Investigator Group
影响因子：
5.6
作者：
Espino Y Sosa S;Flores-Pliego A;Espejel-Nuñez A;Medina-Bastidas D;Vadillo-Ortega F;Zaga-Clavellina V;Estrada-Gutierrez G
通讯作者：
Estrada-Gutierrez G
DOI：
10.1016/0002-9378(89)90665-0
发表时间：
1989-11-01
影响因子：
9.8
作者：
ROBERTS, JM;TAYLOR, RN;MCLAUGHLIN, MK
通讯作者：
MCLAUGHLIN, MK
影响因子：
3.7
作者：
Brew O;Sullivan MH;Woodman A
通讯作者：
Woodman A
影响因子：
5.8
作者：
Rasheeda, K.;Fathima, N. Nishad
通讯作者：
Fathima, N. Nishad