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Differential activa...
Differential activation of placental unfolded protein response pathways implies heterogeneity in causation of early- and late-onset pre-eclampsia
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Yung, Hong Wa (författare)
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Atkinson, Daniel (författare)
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- Campion-Smith, Tim (författare)
- Uppsala universitet,Institutionen för kvinnors och barns hälsa
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- Olovsson, Matts (författare)
- Uppsala universitet,Obstetrik & gynekologi
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Charnock-Jones, D. Stephen (författare)
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Burton, Graham J. (författare)
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(creator_code:org_t)
- 2014-08-06
- 2014
- Engelska.
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 234:2, s. 262-276
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https://uu.diva-port... (primary) (Raw object)
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Based on gestational age at diagnosis and/or delivery, pre-eclampsia (PE) is commonly divided into early-onset (<34 weeks) and late-onset (>= 34 weeks) forms. Recently, the distinction between 'placental' and 'maternal' causation has been proposed, with 'placental' cases being more frequently associated with early-onset and intrauterine growth restriction. To test whether molecular placental pathology varies according to clinical presentation, we investigated stress-signalling pathways, including unfolded protein response (UPR) pathways, MAPK stress pathways, heat-shock proteins and AMPK.. in placentae delivered by caesarean section for clinical indications at different gestational ages. Controls included second-trimester, pre-term and normal-term placentae. BeWo cells were used to investigate how these pathways react to different severities of hypoxia-reoxygenation (H/R) and pro-inflammatory cytokines. Activation of placental UPR and stress-response pathways, including P-IRE1 alpha, ATF6, XBP-1, GRP78 and GRP94, P-p38/p38 and HSP70, was higher in early-onset PE than in both late-onset PE and normotensive controls (NTCs), with a clear inflection around 34 weeks. Placentae from >= 34 weeks PE and NTC were indistinguishable. Levels of UPR signalling were similar between second-trimester and term controls, but were significantly higher in pre-term 'controls' delivered vaginally for chorioamnionitis and other conditions. Severe H/R (1/20% O-2) induced equivalent activation of UPR pathways, including P-eIF2 alpha, ATF6, P-IRE1 alpha, GRP78 and GRP94, in BeWo cells. By contrast, the pro-inflammatory cytokines TNF alpha and IL-1 beta induced only mild activation of P-eIF2 alpha and GRP78. AKT, a central regulator of cell proliferation, was reduced in the <34 weeks PE placentae and severe H/R-treated cells, but not in other conditions. These findings provide the first molecular evidence that placental stress may contribute to the pathophysiology of early-onset pre-eclampsia, whereas that is unlikely to be the case in the late-onset form of the syndrome. (c) 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- placenta
- pre-eclampsia
- pregnancy
- growth restriction
- cell stress responses
- unfolded protein response
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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