The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway

Abstract Preeclampsia (PE) is commonly considered as a placental disorder in pregnancy. Until now, the etiology and pathological mechanism of PE have remained ambiguous. Although PE can lead to a variety of maternal and infant complications, there are still no effective treatments. This study aimed...

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Autores principales:	Ting Li, Zhonghui Ling, Kaipeng Xie, Yixiao Wang, Zhijing Miao, Xiaohong Ji, Jingyun Li, Wenwen Hou, Qiuqin Tang, Xiaojie Yuan, Nan Li, Chanjuan Li, Hongjuan Ding
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f943c0babf7c46a1923ef70fc588dfc5
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spelling	oai:doaj.org-article:f943c0babf7c46a1923ef70fc588dfc52021-12-02T18:49:21ZThe COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway10.1038/s41598-021-94801-52045-2322https://doaj.org/article/f943c0babf7c46a1923ef70fc588dfc52021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94801-5https://doaj.org/toc/2045-2322Abstract Preeclampsia (PE) is commonly considered as a placental disorder in pregnancy. Until now, the etiology and pathological mechanism of PE have remained ambiguous. Although PE can lead to a variety of maternal and infant complications, there are still no effective treatments. This study aimed to explore the correlation between the novel polypeptide COL-4A1 and PE, and to identify the underlying mechanism by which this polypeptide may function and to explore new therapeutic targets for PE. A rat model of PE was established and used to verify the function of the polypeptide COL-4A1 in vivo. Additionally, human umbilical vascular endothelial cells (HUVECs) were cultured with or without COL-4A1 and TNF-α (20 ng/ml). Cell Counting Kit-8 (CCK-8), wound-healing, Transwell and tube formation assays were used to evaluate cell proliferation, migration and angiopoiesis. RNA sequencing and mass spectrometry were conducted to explore the underlying downstream mechanism of COL-4A1. In vivo, COL-4A1 increased blood pressure and elevated the risk of fetal growth restriction (FGR) which was induced by lipopolysaccharide (LPS) in the rat model. In vitro, COL-4A1 significantly inhibited the proliferation and migration of HUVECs. After culture with COL-4A1, compared to control group the adhesive ability and level of reactive oxygen species (ROS) were enhanced and tube formation ability was decreased. Furthermore, Western blotting (WB) and pull-down assays were conducted to explore the underlying mechanism by which COL-4A1 functions, and the TGF-β/PI3K/AKT pathway was identified as the potential pathway involved in its effects. In summary, these results revealed that the polypeptide COL-4A1 caused PE-like symptoms in cells and a rat model. Through the TGF-β/PI3K/AKT pathway, COL-4A1 interferes with the pathogenesis of PE. Thus COL-4A1 is expected to become a potential target of PE, providing a basis for exploring the treatment of PE.Ting LiZhonghui LingKaipeng XieYixiao WangZhijing MiaoXiaohong JiJingyun LiWenwen HouQiuqin TangXiaojie YuanNan LiChanjuan LiHongjuan DingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ting Li Zhonghui Ling Kaipeng Xie Yixiao Wang Zhijing Miao Xiaohong Ji Jingyun Li Wenwen Hou Qiuqin Tang Xiaojie Yuan Nan Li Chanjuan Li Hongjuan Ding The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway
description	Abstract Preeclampsia (PE) is commonly considered as a placental disorder in pregnancy. Until now, the etiology and pathological mechanism of PE have remained ambiguous. Although PE can lead to a variety of maternal and infant complications, there are still no effective treatments. This study aimed to explore the correlation between the novel polypeptide COL-4A1 and PE, and to identify the underlying mechanism by which this polypeptide may function and to explore new therapeutic targets for PE. A rat model of PE was established and used to verify the function of the polypeptide COL-4A1 in vivo. Additionally, human umbilical vascular endothelial cells (HUVECs) were cultured with or without COL-4A1 and TNF-α (20 ng/ml). Cell Counting Kit-8 (CCK-8), wound-healing, Transwell and tube formation assays were used to evaluate cell proliferation, migration and angiopoiesis. RNA sequencing and mass spectrometry were conducted to explore the underlying downstream mechanism of COL-4A1. In vivo, COL-4A1 increased blood pressure and elevated the risk of fetal growth restriction (FGR) which was induced by lipopolysaccharide (LPS) in the rat model. In vitro, COL-4A1 significantly inhibited the proliferation and migration of HUVECs. After culture with COL-4A1, compared to control group the adhesive ability and level of reactive oxygen species (ROS) were enhanced and tube formation ability was decreased. Furthermore, Western blotting (WB) and pull-down assays were conducted to explore the underlying mechanism by which COL-4A1 functions, and the TGF-β/PI3K/AKT pathway was identified as the potential pathway involved in its effects. In summary, these results revealed that the polypeptide COL-4A1 caused PE-like symptoms in cells and a rat model. Through the TGF-β/PI3K/AKT pathway, COL-4A1 interferes with the pathogenesis of PE. Thus COL-4A1 is expected to become a potential target of PE, providing a basis for exploring the treatment of PE.
format	article
author	Ting Li Zhonghui Ling Kaipeng Xie Yixiao Wang Zhijing Miao Xiaohong Ji Jingyun Li Wenwen Hou Qiuqin Tang Xiaojie Yuan Nan Li Chanjuan Li Hongjuan Ding
author_facet	Ting Li Zhonghui Ling Kaipeng Xie Yixiao Wang Zhijing Miao Xiaohong Ji Jingyun Li Wenwen Hou Qiuqin Tang Xiaojie Yuan Nan Li Chanjuan Li Hongjuan Ding
author_sort	Ting Li
title	The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway
title_short	The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway
title_full	The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway
title_fullStr	The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway
title_full_unstemmed	The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway
title_sort	col-4a1 polypeptide destroy endothelial cells through the tgf-β/pi3k/akt pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f943c0babf7c46a1923ef70fc588dfc5
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The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway

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