Abstract
Preeclampsia (PE) is a severe pregnancy disorder caused by placental dysfunction. Protein O-fucosylation is a type of protein post translational modification that is catalyzed by protein O-fucosyltransferases (poFUTs). However, the role and underlying mechanisms of O-fucosylation/poFUT1 in PE remain elusive. Here, we revealed a lower level of poFUT1 in the plasma and placental tissues of PE patients than in normal pregnancy (NP) women. Moreover, poFUT1 deletion induced PE-like phenotypes in a mouse model. Mechanistically, we globally screened O-fucosylated proteins and identified EDIL3 with an O-fucosylation site at threonine 88. Furthermore, O-fucosylation-EDIL3 can directly interact with LIFR on trophoblasts, consequently activating the STAT3 signaling pathway, promoting the invasion and vascular remodeling ability of trophoblasts. Conversely, de-O-fucosylation-EDIL3 aggravated PE-like phenotypes by attenuating placental development in vitro and in vivo. Our data elucidate the function of poFUT1/O-fucosylation EDIL3/LIFR axis during placental development, providing glycol-based target for diagnostic and therapeutic of preeclampsia.
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Acknowledgements
We thank Prof. Heng Yin and Prof. Xiaochen Jia (Dalian Institute of Chemical Physics, Chinese Academy of Sciences) for enzymatic reaction detection. This work was supported by the National Natural Science Foundation of China (no. 32271335).
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Li, Y., Wu, H., Lei, Y. et al. Defective O-fucosylation of EDIL3 attenuates invasion and vascular remodeling of trophoblasts via LIFR signaling pathway in preeclampsia. Nat Commun (2026). https://doi.org/10.1038/s41467-026-73139-4
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DOI: https://doi.org/10.1038/s41467-026-73139-4
