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Neuregulin-1-mediat...
Neuregulin-1-mediated ErbB2-ErbB3 signalling protects human trophoblasts against apoptosis to preserve differentiation
- Artikel/kapitelEngelska2015
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2015-01-01
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The Company of Biologists,2015
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:132602398
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http://kipublications.ki.se/Default.aspx?queryparsed=id:132602398URI
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https://doi.org/10.1242/jcs.176933DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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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.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Plessl, K
(författare)
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Draxler, P
(författare)
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Otti, GR
(författare)
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Fiala, CKarolinska Institutet
(författare)
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Knofler, M
(författare)
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Pollheimer, J
(författare)
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Karolinska Institutet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of cell science: The Company of Biologists128:23, s. 4306-43161477-91370021-9533
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