High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts
Abstract Hyperlipidemia contributes to low-grade inflammation and abnormal immune response, which is putatively involved in the development of pre-eclampsia (PE). As components of innate immune system, complements play a critical role in regulating inflammation. However, how cell-autonomous compleme...
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| Format: | Article |
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Nature Portfolio
2025-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08298-z |
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| author | Simeng Zhu Siyue Chen Yingzhou Ge Fangyue Zhou Kaizhen Su Congfeng Xu Yanting Wu Hefeng Huang |
| author_facet | Simeng Zhu Siyue Chen Yingzhou Ge Fangyue Zhou Kaizhen Su Congfeng Xu Yanting Wu Hefeng Huang |
| author_sort | Simeng Zhu |
| collection | DOAJ |
| description | Abstract Hyperlipidemia contributes to low-grade inflammation and abnormal immune response, which is putatively involved in the development of pre-eclampsia (PE). As components of innate immune system, complements play a critical role in regulating inflammation. However, how cell-autonomous complement changes and works in PE remains elusive. In the current study, we established L-NAME-induced mice to manifest PE-like symptoms. In presence of high-fat diet (HFD) feeding, the PE-like symptoms were considerably aggravated, as well as down-regulated complement C3 in HFD/L-NAME mice trophoblasts. To explore the effect of C3 in PE development, we generated C3 overexpression and knockdown cell (Swan.71C3 and Swan.71ΔC3) based on Swan.71, a trophoblast cell line. We found that Swan.71C3 cells display promoted proliferation, migration and invasion capability and less secretion of anti-angiogenetic cytokines, while Swan.71ΔC3 showed highly-activated NLRP3 inflammasome and pyroptosis, which was also noted in HFD/L-NAME placentas, highlighting the contributing role of inflammation to PE. Indeed, pro-inflammatory cytokines were increased in placentas from HFD/L-NAME mice. The similar trends of C3 in trophoblast from severe PE patients supported the contribution role of C3 to PE pathogenesis. Thus, our study provides evidence that cell-autonomous complement C3 regulates NLRP3 inflammasome activation upon HFD exposure, affecting trophoblast cell function in PE development. |
| format | Article |
| id | doaj-art-8450eb6e022743f4bb6dde4daf4d0a00 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
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| series | Communications Biology |
| spelling | doaj-art-8450eb6e022743f4bb6dde4daf4d0a002025-08-20T03:26:47ZengNature PortfolioCommunications Biology2399-36422025-06-018111210.1038/s42003-025-08298-zHigh-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblastsSimeng Zhu0Siyue Chen1Yingzhou Ge2Fangyue Zhou3Kaizhen Su4Congfeng Xu5Yanting Wu6Hefeng Huang7Department of Cardiology, Sixth People’s Hospital, Shanghai Jiaotong University School of MedicineObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityKey Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of MedicineDepartment of Cardiology, Sixth People’s Hospital, Shanghai Jiaotong University School of MedicineObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityObstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan UniversityAbstract Hyperlipidemia contributes to low-grade inflammation and abnormal immune response, which is putatively involved in the development of pre-eclampsia (PE). As components of innate immune system, complements play a critical role in regulating inflammation. However, how cell-autonomous complement changes and works in PE remains elusive. In the current study, we established L-NAME-induced mice to manifest PE-like symptoms. In presence of high-fat diet (HFD) feeding, the PE-like symptoms were considerably aggravated, as well as down-regulated complement C3 in HFD/L-NAME mice trophoblasts. To explore the effect of C3 in PE development, we generated C3 overexpression and knockdown cell (Swan.71C3 and Swan.71ΔC3) based on Swan.71, a trophoblast cell line. We found that Swan.71C3 cells display promoted proliferation, migration and invasion capability and less secretion of anti-angiogenetic cytokines, while Swan.71ΔC3 showed highly-activated NLRP3 inflammasome and pyroptosis, which was also noted in HFD/L-NAME placentas, highlighting the contributing role of inflammation to PE. Indeed, pro-inflammatory cytokines were increased in placentas from HFD/L-NAME mice. The similar trends of C3 in trophoblast from severe PE patients supported the contribution role of C3 to PE pathogenesis. Thus, our study provides evidence that cell-autonomous complement C3 regulates NLRP3 inflammasome activation upon HFD exposure, affecting trophoblast cell function in PE development.https://doi.org/10.1038/s42003-025-08298-z |
| spellingShingle | Simeng Zhu Siyue Chen Yingzhou Ge Fangyue Zhou Kaizhen Su Congfeng Xu Yanting Wu Hefeng Huang High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts Communications Biology |
| title | High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts |
| title_full | High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts |
| title_fullStr | High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts |
| title_full_unstemmed | High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts |
| title_short | High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts |
| title_sort | high fat diet induces pre eclampsia through dampening cell autonomous c3 in trophoblasts |
| url | https://doi.org/10.1038/s42003-025-08298-z |
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