4.6 Article

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

期刊

CELL BIOLOGY AND TOXICOLOGY
卷 38, 期 4, 页码 611-628

出版社

SPRINGER
DOI: 10.1007/s10565-021-09636-7

关键词

Preeclampsia; Macrophage polarization; Chemerin; CMKLR1; CEBP alpha; IRF8

资金

  1. Natural Science Foundation of Hubei [2018CFB472]
  2. Top Medical Youth Talent Program in Hubei Province
  3. Luo Yuankai-Zishen Yutaiwan-Research Fund for Young Scholars [20190808]

向作者/读者索取更多资源

The chemerin signaling pathway involving CMKLR1/Akt/CEBP alpha axis plays a crucial role in regulating macrophage polarization and mediating the pathogenic effects of chemerin on preeclampsia. Targeting chemerin signaling may offer potential benefits for the prevention and treatment of preeclampsia.
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/CEBP alpha axis in regulating macrophage polarization and mediating the pathogenic effects of chemerin on preeclampsia. We showed that chemerin, in a dose- and time-dependent manner, stimulated M1 macrophage polarization, inhibited macrophage-induced trophoblast invasion and migration, and suppressed macrophage-mediated angiogenesis. All these chemerin-induced phenotypes are essentially mediated by sequentially CMKLR1, Akt activation, and CEBP alpha. Mechanistically, CEBP alpha acted as a transcriptional activator for both IRF8 and chemerin. In vivo, chemerin aggravated preeclampsia, while alpha-NETA, an inhibitor for CMKLR1, significantly suppressed M1 macrophage polarization and alleviated preeclampsia. In summary, chemerin, by activating CMKLR1/Akt/CEBP alpha axis, forms a positive feedback loop, promotes M1 macrophage polarization, suppresses trophoblast migration/invasion and angiogenesis, and contributes to preeclampsia. Therefore, targeting chemerin signaling may benefit the prevention and/or treatment of preeclampsia.

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