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<p>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&#xa0;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<sup>C3</sup> and Swan.71<sup>ΔC3</sup>) based on Swan.71, a trophoblast cell line. We found that Swan.71<sup>C3</sup> cells display promoted proliferation, migration and invasion capability and less secretion of anti-angiogenetic cytokines, while Swan.71<sup>ΔC3</sup> 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.</p><p></p>

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High-fat diet induces pre-eclampsia through dampening cell-autonomous C3 in trophoblasts

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月6日

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  • Simeng Zhu,
  • Siyue Chen,
  • Yingzhou Ge,
  • Fangyue Zhou,
  • Kaizhen Su,
  • Congfeng Xu,
  • Yanting Wu,
  • Hefeng Huang

摘要

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.