HOXA9-induced chemerin signals through CMKLR1/AMPK/TXNIP/NLRP3 pathway to induce pyroptosis of trophoblasts and aggravate preeclampsia.

Background: Up-regulated chemerin correlates with the risk and the severity of preeclampsia. In this study, we examined impacts and underlying mechanisms by which chemerin regulates pyroptosis and trophoblast inflammation.

Methods: An in vivo preeclampsia model was established in rats and trophoblasts challenged with hypoxia/reoxygenation (H/R) with or without exogenous chemerin were used as the in vitro model.

Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBPɑ axis and inducing M1 macrophage polarization.

A higher ratio of M1/M2 macrophages and an elevated chemerin level are both related to increased risk of preeclampsia. However, the crosstalk between these two events and their collective contribution to preeclampsia are not well understood. In this study, we assessed the impacts of chemerin chemokine-like receptor 1 (CMKLR1)/p-Akt/CEBPα axis in regulating macrophage polarization and mediating the pathogenic effects of chemerin on preeclampsia.