| First Author | Zhu S | Year | 2025 |
| Journal | Commun Biol | Volume | 8 |
| Issue | 1 | Pages | 879 |
| PubMed ID | 40481230 | Mgi Jnum | J:367796 |
| Mgi Id | MGI:8212067 | Doi | 10.1038/s42003-025-08298-z |
| Citation | Zhu S, et al. (2025) High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts. Commun Biol 8(1):879 |
| abstractText | 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.71(C3) and Swan.71(DeltaC3)) based on Swan.71, a trophoblast cell line. We found that Swan.71(C3) cells display promoted proliferation, migration and invasion capability and less secretion of anti-angiogenetic cytokines, while Swan.71(DeltaC3) 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. |
