Elabela: Negative Regulation of Ferroptosis in Trophoblasts via the Ferritinophagy Pathway Implicated in the Pathogenesis of Preeclampsia

作者全名："Yang, Huan; Zhang, Xuemei; Ding, Yubin; Xiong, Hui; Xiang, Shaojian; Wang, Yang; Li, Huanhuan; Liu, Zheng; He, Jie; Tao, Yuelan; Yang, Hongbing; Qi, Hongbo"

作者地址："[Yang, Huan; Xiong, Hui; Xiang, Shaojian; Yang, Hongbing] Chongqing Univ Three Gorges Hosp, Dept Obstet, Chongqing 404100, Peoples R China; [Yang, Huan; Zhang, Xuemei; Ding, Yubin; Wang, Yang; Liu, Zheng; He, Jie; Tao, Yuelan; Qi, Hongbo] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Minist Educ China, Chongqing 400016, Peoples R China; [Zhang, Xuemei; Wang, Yang; Liu, Zheng; He, Jie; Tao, Yuelan] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet, Chongqing 400016, Peoples R China; [Ding, Yubin; Qi, Hongbo] Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, Chongqing 401147, Peoples R China; [Li, Huanhuan] Chongqing Univ Three Gorges Hosp, Dept Emergency, Chongqing 404100, Peoples R China"

通信作者："Yang, HB (通讯作者)，Chongqing Univ Three Gorges Hosp, Dept Obstet, Chongqing 404100, Peoples R China.; Qi, HB (通讯作者)，Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Minist Educ China, Chongqing 400016, Peoples R China.; Qi, HB (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, Chongqing 401147, Peoples R China."

来源：CELLS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000909288500001

JCR分区：Q2

影响因子：5.1

年份：2023

卷号：12

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：preeclampsia; trophoblast; Elabela; ferroptosis; ferritinophagy

摘要："Preeclampsia is a leading contributor to increased maternal morbidity and mortality in the perinatal period. Increasing evidence demonstrates that ferroptosis is an essential mechanism for the pathogenesis of preeclampsia. Elabela is a novel small-molecule polypeptide, mainly expressed in embryonic and transplacental tissues, with an ability to promote cell proliferation and invasion. However, its specific regulatory mechanism in preeclampsia has not been completely elucidated. In this study, we first reveal an increased grade of ferroptosis accompanied by a downregulation of the expression of Elabela in preeclampsia placentas. We then confirm the presence of a ferroptosis phenotype in the placenta of the mouse PE-like model, and Elabela can reduce ferroptosis in the placenta and improve adverse pregnancy outcomes. Furthermore, we demonstrate that targeting Elabela alleviates the cellular dysfunction mediated by Erastin promoting increased lipid peroxidation in vitro. Subsequent mechanistic studies suggest that Elabela increases FTH1 levels by inhibiting the ferritinophagy pathway, and consequently chelates the intracellular labile iron pool and eventually arrests ferroptosis. In conclusion, Elabela deficiency exacerbates ferroptosis in the placenta, which is among the potential mechanisms in the pathogenesis of preeclampsia. Targeting the Elabela-ferritinophagy-ferroptosis signaling axis provides a new therapeutic intervention strategy to alleviate preeclampsia."

基金机构：National Natural Science Foundation of China; Chongqing Science and Technology Commission; Wanzhou Science and Technology Commission; [82171679]; [82171664]; [2022NSCQ-MSX5209]

基金资助正文："This work was supported by The National Natural Science Foundation of China (No. 82171679, 82171664), Chongqing Science and Technology Commission (No. 2022NSCQ-MSX5209), and Wanzhou Science and Technology Commission (No. wzstc-kw2022003)."