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Low-Density Lipoprotein Receptor-Related Protein 6 Is Essential for Trophoblast Survival and Invasion

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Abstract

Remodeling of maternal spiral artery after the implantation of embryo relies on tightly regulated trophoblast functions and is pivotal to ensure the success of pregnancy. Low-density lipoprotein receptor-related protein 6 (LRP6) is implicated in angiogenesis and several vascular diseases, but its function in trophoblast regulation is still not fully understood. We aimed to investigate the involvement of LRP6 in trophoblast functions during maternal spiral artery remodeling. HTR-8/SVneo cells, a trophoblast cell line, were employed to examine the impact of LRP6 knockdown on proliferation, apoptosis, and migration, as well as invasion and tube formation. Expression of matrix metalloproteinases (MMPs), angiogenic factors placental growth factor (PlGF), and vascular endothelial growth factor (VEGF), as well as activation of canonical Wnt/β-catenin signaling pathway, which was involved in artery remodeling process, was also analyzed. Lipoprotein receptor-related protein 6 knockdown suppressed proliferation, migration, invasion, and tube formation, as well as induced apoptosis in HTR-8/SVneo cells. In addition, LRP6 knockdown also significantly decreased expression of MMPs, PlGF, and VEGF and activation of Wnt/β-catenin signaling pathway. Lipoprotein receptor-related protein 6 might positively regulate the remodeling of the maternal artery through both endovascular formation and trophoblast invasion.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Shandong Provincial Hospital Affiliated to Shandong University, No 324 Jingwu Road, Jinan, 250021, China

    Lei Li MD, Jipeng Wan MD, Jing Xue MD, Hongyan Li MD, Shan Wang MD, Qian Zhou MD, Yu Zhou MD & Xietong Wang MD, PhD

  2. Key Laboratory of Birth Regulation and Control Technology of National Health and Family Planning Commission of China, Jinan, 250025, China

    Xietong Wang MD, PhD

  3. Maternal and Child Health Care of Shandong Province, Jinan, 250025, China

    Xietong Wang MD, PhD

Authors
  1. Lei Li MD
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  2. Jipeng Wan MD
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  3. Jing Xue MD
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  4. Hongyan Li MD
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  5. Shan Wang MD
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  6. Qian Zhou MD
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  7. Yu Zhou MD
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  8. Xietong Wang MD, PhD
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Correspondence to Jipeng Wan MD or Xietong Wang MD, PhD.

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Li, L., Wan, J., Xue, J. et al. Low-Density Lipoprotein Receptor-Related Protein 6 Is Essential for Trophoblast Survival and Invasion. Reprod. Sci. 26, 35–43 (2019). https://doi.org/10.1177/1933719118756773

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  • DOI: https://doi.org/10.1177/1933719118756773

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