期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 23, 页码 4306-4316出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.176933
关键词
Trophoblast; Neuregulin 1; ErbB2; ErbB3; Apoptosis; Differentiation
类别
资金
- Austrian Science Fund [P-25187-B13]
- Austrian Science Fund (FWF) [P 25187] Funding Source: researchfish
- Austrian Science Fund (FWF) [P25187] Funding Source: Austrian Science Fund (FWF)
During placentation, foetal trophoblasts invade deeply into maternal tissue to establish a foeto-maternal circulation. We have previously shown that extravillous trophoblast (EVT) lineage cells express ErbB2 and ErbB3, of which the potential as an oncogenic unit is well established. However, a physiological function of this receptor combination in humans remains a puzzling question. Here, we demonstrate neuregulin 1 (NRG1) expression and secretion by human decidual stromal cells. Stimulation of human primary trophoblasts with exogenous NRG1 induced phosphorylation of ErbB2, ErbB3 and related downstream effectors. Co-immunoprecipitation experiments confirmed the formation of ErbB2-ErbB3 dimers upon ligand engagement. Along this line, receptor knockdown and ErbB3 neutralization strongly diminished NRG1-dependent activation of the signalling complex. Functional studies revealed that NRG1 promotes EVT formation in placental explant cultures. Although, in the presence of NRG1, basal and camptothecin-induced trophoblast apoptosis was significantly repressed, this effect was abolished upon ErbB3 inhibition. Notably, camptothecin provoked a strong reduction of trophoblast cell column size, whereas NRG1-treated explants were refractory to the compound. Taken together, our findings newly identify a physiological function of the NRG1-ErbB2-ErbB3 axis in trophoblast survival during human placental development.
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