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Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts

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 pr...

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Autores principales: Feng, Yinglin, Chen, Xia, Wang, Huiqiao, Chen, Xueping, Lan, Zixin, Li, Pan, Cao, Yingshi, Liu, Mian, Lv, Jin, Chen, Yun, Wang, Yu, Sheng, Chao, Huang, Yingying, Zhong, Mei, Wang, Zhijian, Yue, Xiaojing, Huang, Liping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378400/
https://www.ncbi.nlm.nih.gov/pubmed/34421817
http://dx.doi.org/10.3389/fendo.2021.664766
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author Feng, Yinglin
Chen, Xia
Wang, Huiqiao
Chen, Xueping
Lan, Zixin
Li, Pan
Cao, Yingshi
Liu, Mian
Lv, Jin
Chen, Yun
Wang, Yu
Sheng, Chao
Huang, Yingying
Zhong, Mei
Wang, Zhijian
Yue, Xiaojing
Huang, Liping
author_facet Feng, Yinglin
Chen, Xia
Wang, Huiqiao
Chen, Xueping
Lan, Zixin
Li, Pan
Cao, Yingshi
Liu, Mian
Lv, Jin
Chen, Yun
Wang, Yu
Sheng, Chao
Huang, Yingying
Zhong, Mei
Wang, Zhijian
Yue, Xiaojing
Huang, Liping
author_sort Feng, Yinglin
collection PubMed
description 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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spelling pubmed-83784002021-08-21 Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts Feng, Yinglin Chen, Xia Wang, Huiqiao Chen, Xueping Lan, Zixin Li, Pan Cao, Yingshi Liu, Mian Lv, Jin Chen, Yun Wang, Yu Sheng, Chao Huang, Yingying Zhong, Mei Wang, Zhijian Yue, Xiaojing Huang, Liping Front Endocrinol (Lausanne) Endocrinology 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. Frontiers Media S.A. 2021-08-06 /pmc/articles/PMC8378400/ /pubmed/34421817 http://dx.doi.org/10.3389/fendo.2021.664766 Text en Copyright © 2021 Feng, Chen, Wang, Chen, Lan, Li, Cao, Liu, Lv, Chen, Wang, Sheng, Huang, Zhong, Wang, Yue and Huang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Feng, Yinglin
Chen, Xia
Wang, Huiqiao
Chen, Xueping
Lan, Zixin
Li, Pan
Cao, Yingshi
Liu, Mian
Lv, Jin
Chen, Yun
Wang, Yu
Sheng, Chao
Huang, Yingying
Zhong, Mei
Wang, Zhijian
Yue, Xiaojing
Huang, Liping
Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts
title Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts
title_full Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts
title_fullStr Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts
title_full_unstemmed Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts
title_short Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts
title_sort collagen i induces preeclampsia-like symptoms by suppressing proliferation and invasion of trophoblasts
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378400/
https://www.ncbi.nlm.nih.gov/pubmed/34421817
http://dx.doi.org/10.3389/fendo.2021.664766
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