Journal
PLACENTA
Volume 83, Issue -, Pages 8-16Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.placenta.2019.06.375
Keywords
HIF-1a; TLR4 signaling; Placental microvascular endothelial cell; Preeclampsia
Funding
- Guangdong Province Science and technology Projects [2018KJYZ015, 2017ZC0319]
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Objective: Hypoxia-induced factor 1a (HIF-1a) and Toll-like receptor 4 (TLR4) are involved in pre-eclampsia (PE) pathogenesis. However, little is known about their relationships. This study aimed to investigate the interaction of HIF-1a and TLR4 in PE pathogenesis. Methods: The expression of HIF-1a and TLR4 were analyzed by qRT-PCR. Celluar PE model was established by hypoxia/reoxygenation treatment of human placental microvascular endothelial cells (hPMEC). Cell proliferation, apoptosis, invasion and migration were analyzed by CCK-8, flow cytometry, Transwell and scratch adhesion test, respectively. Angiogenesis was performed by tube formation, Ang-1 in culture supernatant was analyzed by ELISA. Results: HIF-1a and TLR4 expression were significantly elevated in placental tissues from early-onset and lateonset severe pre-eclampsia patients compared with control, with increased Bax, TRIF and PUMA, and decreased Bcl-2 and VEGFA; Down-regulation of HIF-1a expression decreased TLR4 expression, promoted proliferation, invasion, migration and angiogenesis but suppressed apoptosis in cellular model. In addition, silencing HIF-1a and TAK232 treatment synergically promoted some more proliferation, invasion, migration and angiogenesis but suppressed apoptosis in cellular model. Conclusion: HIF-1a could promote hPMEC apoptosis by regulating TLR4 expression during PE pathogenesis.
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