MedElevator
Войти в исследования Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Oleanolic acid derivative OA17 inhibits trophoblast apoptosis by suppressing HIF-1α nuclear translocation in SLE-associated adverse pregnancy outcomes.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhou Mengqi, Jin Lin, Wang Pan, Sun Chenlong, Fang Shuqi, Chen Yu, Tang Yujing, Geng Shuo, Liu Lianghu, Zhang Han, Yang Yi'ning, Liu Qinyu, He Wenping, Zhang Tianjing, Zhao Yuchen, Xu Li, Tao Li, Zhao Tianyuan, Zhang Xianzheng, Zhang Lingling
Аннотация
BACKGROUND: Systemic lupus erythematosus (SLE) primarily affects women of reproductive age and is associated with a high incidence of adverse pregnancy outcomes (APOs). Recent studies reveal that elevated HIF-1α expression in the placenta is involved in SLE-associated APOs and multiple pregnancy complications, but no clinically approved HIF-1α inhibitors exist to mitigate APOs. OA17, a pentacyclic triterpenoid derived from structural modification of oleanolic acid (OA), exhibits potent anti-inflammatory and antioxidant properties. However, OA17 function and the underlying mechanisms in SLE pregnancy outcomes remain unclear.
PURPOSE: The aim of this study was to explore the role of HIF-1α in SLE-associated APOs and to assess the therapeutic potential of OA17 as a novel treatment.
METHODS: Human placental samples and relevant clinical data were collected from participants to explore the mechanisms SLE-associated APOs. Additionally, HTR-8/SVneocells, an Extravillous trophoblast (EVT)-immortalized cell line, were subjected to hypoxia (1 % O₂) and chemicals known to stabilize HIF-1α (CoCl2 and DMOG) to mimic the upregulation of HIF-1α observed in SLE pregnancies. The relationship between HIF-1α and oxidative stress/apoptosis in the HTR-8/SVneo cells was explored through H2O2 stimulation, sh-HIF-1α, and CUT-TAG assay. Additionally, HTR-8/SVneo was treated with OA17 and pregnant MRL-lpr mice received continuous OA17 over two weeks.
RESULTS: We demonstrated that significantly increased levels of HIF-1α and heightened apoptosis in EVT cells within the placental tissues of SLE pregnancies. Mechanistically, HIF-1α bound to the SOD2 promoter to repress SOD2 transcription and regulate ROS to promote apoptosis. OA17 treatment in lupus-prone MRL/lpr mice alleviated renal injury, reduced oxidative stress and hypoxia-induced apoptosis in EVT cells by inhibiting HIF-1α nuclear translocation, thus improving APOs. In addition, OA17 treatment attenuated the biological functions of hypoxia-impaired EVT cells, including cell proliferation, invasion, and migration.
CONCLUSION: Our data suggest that elevated HIF-1α during SLE pregnancies can be considered a contributing factor to APOs, OA17 inhibits trophoblast apoptosis by suppressing HIF-1α nuclear translocation in SLE-associated APOs. OA17 could be a potential new drug for other pregnancy complications in the clinic.
PURPOSE: The aim of this study was to explore the role of HIF-1α in SLE-associated APOs and to assess the therapeutic potential of OA17 as a novel treatment.
METHODS: Human placental samples and relevant clinical data were collected from participants to explore the mechanisms SLE-associated APOs. Additionally, HTR-8/SVneocells, an Extravillous trophoblast (EVT)-immortalized cell line, were subjected to hypoxia (1 % O₂) and chemicals known to stabilize HIF-1α (CoCl2 and DMOG) to mimic the upregulation of HIF-1α observed in SLE pregnancies. The relationship between HIF-1α and oxidative stress/apoptosis in the HTR-8/SVneo cells was explored through H2O2 stimulation, sh-HIF-1α, and CUT-TAG assay. Additionally, HTR-8/SVneo was treated with OA17 and pregnant MRL-lpr mice received continuous OA17 over two weeks.
RESULTS: We demonstrated that significantly increased levels of HIF-1α and heightened apoptosis in EVT cells within the placental tissues of SLE pregnancies. Mechanistically, HIF-1α bound to the SOD2 promoter to repress SOD2 transcription and regulate ROS to promote apoptosis. OA17 treatment in lupus-prone MRL/lpr mice alleviated renal injury, reduced oxidative stress and hypoxia-induced apoptosis in EVT cells by inhibiting HIF-1α nuclear translocation, thus improving APOs. In addition, OA17 treatment attenuated the biological functions of hypoxia-impaired EVT cells, including cell proliferation, invasion, and migration.
CONCLUSION: Our data suggest that elevated HIF-1α during SLE pregnancies can be considered a contributing factor to APOs, OA17 inhibits trophoblast apoptosis by suppressing HIF-1α nuclear translocation in SLE-associated APOs. OA17 could be a potential new drug for other pregnancy complications in the clinic.