Neuregulin-1-mediated ErbB2-ErbB3 signalling protects human trophoblasts against apoptosis to preserve differentiation

Fock, V (author)

Plessl, K (author)

Draxler, P (author)

Otti, GR (author)

Knofler, M (author)

Pollheimer, J (author)

(creator_code:org_t)

2015-01-01
2015
English.
In: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 128:23, s. 4306-4316

Related links:: https://jcs.biologis...; show more...; http://kipublication...; https://doi.org/10.1...; show less...

Abstract Subject headings

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/ErbB3, whose potential as oncogenic unit is well established. However, a physiological function of this receptor combination in humans remains a puzzling question. Here we could demonstrate neuregulin (NRG) 1 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 knockdowns and ErbB3 neutralization strongly diminished NRG1-dependent activation of the signalling unit. Functional studies revealed that NRG1 promotes EVT formation in placental explant cultures. While 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 columns in size, whereas NRG1-treated explants were refractory to the compound. Together, our findings highlight a novel physiological function of the NRG1/ErbB2/ErbB3 axis in trophoblast survival during human placental development.

By the author/editor: Fock, V; Plessl, K; Draxler, P; Otti, GR; Fiala, C; Knofler, M; show more...; Pollheimer, J; show less...

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