SIRT1-NCOR2-corepressor moduleert trofoblast-macrofaaginteracties bij pre-eclampsie

BACKGROUND:Preeclampsia is a severe hypertensive disorder of pregnancy associated with lowSIRT1(sirtuin 1) levels in trophoblasts. Single-cell sequencing showed abnormal activation of trophoblastRarres2(retinoic acid receptor responder 2) and macrophageCmklr1(chemokine-like receptor 1) at the maternal-fetal interface in systemicSirt1heterozygous knockout mice. This study investigated how low SIRT1 in trophoblasts increases RARRES2 expression, affecting macrophage polarization and preeclampsia pathogenesis.METHODS:We conducted coculture experiments to analyze trophoblast RARRES2 and macrophage CMKLR1 interactions, performed luciferase and chromatin immunoprecipitation assays to validate transcription factors for RARRES2 in trophoblasts, and utilized mass spectrometry and immunoprecipitation to identify transcriptional coregulators. cKO (trophoblast-specificSirt1knockout) mice were generated and treated withRarres2knockout or progesterone supplementation to validate the role of the SIRT1