Lina Zhao1, Ruixia Ma1, Li Zhang1, Xiaolan Yuan1, Jinhua Wu1, Lirong He1, Guocheng Liu2, Rui Du3. 1. Department of Obstetrics, Guangdong Woman and Children Hospital, Guangzhou, Guangdong, China. 2. Department of Obstetrics, Guangdong Woman and Children Hospital, Guangzhou, Guangdong, China. Electronic address: hnliuguocheng@126.com. 3. Depaertment of Pathology, Guangdong Woman and Children Hospital, Guangzhou, Guangdong, China. Electronic address: Xzf192@sohu.com.
Abstract
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 late-onset 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.
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 late-onset severe pre-eclampsiapatients 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.
Authors: Miguel A Ortega; Miguel A Saez; Oscar Fraile-Martínez; Ángel Asúnsolo; Leonel Pekarek; Coral Bravo; Santiago Coca; Felipe Sainz; Melchor Álvarez- Mon; Julia Buján; Natalio García-Honduvilla Journal: Int J Mol Sci Date: 2020-04-03 Impact factor: 5.923