Scientific Reports (Aug 2021)

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

  • 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

DOI
https://doi.org/10.1038/s41598-021-94801-5
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 10

Abstract

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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.