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• W2394501384 abstract "Rationale: We hypothesized that cluster of differentiation 74 (CD74) downregulation on placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. Objective: Preeclamptic pregnancies feature hypertension, proteinuria, and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies. Methods and Results: We performed whole-genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By reverse transcriptase-polymerase chain reaction, we confirmed this finding in early-onset (<34 gestational week, n=26) and late-onset (≥34 gestational week, n=24) samples from preeclamptic women, compared with healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry, and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared with controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM , ICAM4 , and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naive and activated macrophages lacking CD74 showed a shift toward a proinflammatory signature with an increased secretion of tumor necrosis factor-α, chemokine (C–C motif) ligand 5, and monocyte chemotactic protein-1, when cocultured with trophoblasts compared with control macrophages. Trophoblasts stimulated by these factors express more CYP2J2 , sFlt1 , TNFα , and IL-8 . CD74-knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas, and impaired spiral artery remodeling with fetal growth restriction. Conclusions: CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation toward a proinflammatory signature and a disturbed crosstalk with trophoblasts." @default.
• W2394501384 created "2016-06-24" @default.
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• W2394501384 date "2016-06-24" @default.
• W2394501384 modified "2023-10-14" @default.
• W2394501384 title "CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia" @default.
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• W2394501384 doi "https://doi.org/10.1161/circresaha.116.308304" @default.
• W2394501384 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5578411" @default.
• W2394501384 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27199465" @default.
• W2394501384 hasPublicationYear "2016" @default.
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