The role of autocine TGFb1 in endothelial cell activation induced by phagocytosis of necrotic trophoblasts: a possible role in the pathogenesis of pre-eclampsia.

Show simple item record Chen, Qi en Chen, L en Liu, Bonnia en Vialli, C en Stone, Peter en Ching, Lai-Ming en Chamley, Lawrence en 2011-11-07T19:42:18Z en 2010 en
dc.identifier.citation Journal of Pathology 221(1):87-95 2010 en
dc.identifier.issn 0022-3417 en
dc.identifier.uri en
dc.description.abstract Pre-eclampsia is a disorder of pregnancy characterized by hypertension and endothelial cell dysfunction. The causes of pre-eclampsia are unclear but it is proposed that a factor released from the placenta triggers the maternal symptoms. One possible triggering factor is dead trophoblasts that are shed from the placenta, then deported to become trapped in the maternal pulmonary capillaries. It is hypothesized that trophoblasts die by apoptosis in normal pregnancy, but by necrosis in pre-eclampsia. Deported trophoblasts may be phagocytosed by the pulmonary endothelial cells and we have previously shown that phagocytosis of necrotic trophoblasts leads to the activation of endothelial cells, accompanied by the release of interleukin-6 from these cells. However, the mechanistic pathway linking phagocytosis of necrotic trophoblasts and endothelial cell activation is unknown. Here we show that, after phagocytosis of necrotic, but not apoptotic, trophoblasts, endothelial cells secrete TGFβ1. Using recombinant endoglin to inhibit the function of TGFβ1 we have shown that the TGFβ1 does not directly activate endothelial cells but rather it induces endothelial IL-6 secretion. The IL-6 then induces endothelial cell activation. Inhibiting either TGFβ1 or IL-6 prevented endothelial cell activation in response to phagocytosing necrotic trophoblasts, but inhibiting IL-6 did not prevent secretion of TGFβ1, confirming the order of signalling. IL-6 also reduced endothelial cell-surface endoglin but increased the amount of soluble endoglin released from placental explants. These interactions between the IL-6 and TGFβ1 pathways in both the endothelium and placenta may help to regulate the maternal response to deported trophoblasts in pregnancy. Copyright © 2010 Pathological Society of Great Britain and Ireland. en
dc.language EN en
dc.publisher John Wiley & Sons, Ltd. en
dc.relation.ispartofseries Journal of Pathology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.subject pre-eclampsia en
dc.subject TGF beta en
dc.subject IL-6 en
dc.subject trophoblast en
dc.subject endothelial en
dc.subject CLARK ET-AL en
dc.subject SOLUBLE ENDOGLIN en
dc.subject MULTIPLE-MYELOMA en
dc.subject MATERNAL DEATH en
dc.subject PLASMA-LEVELS en
dc.subject INTERLEUKIN-6 en
dc.subject GROWTH en
dc.subject WOMEN en
dc.subject CYTOKINES en
dc.subject BETA en
dc.title The role of autocine TGFb1 in endothelial cell activation induced by phagocytosis of necrotic trophoblasts: a possible role in the pathogenesis of pre-eclampsia. en
dc.type Journal Article en
dc.identifier.doi 10.1002/path.2690 en
pubs.issue 1 en
pubs.begin-page 87 en
pubs.volume 221 en
dc.rights.holder Copyright: Pathological Society of Great Britain and Ireland en
dc.identifier.pmid 20217871 en
pubs.end-page 95 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 101721 en Medical and Health Sciences en Medical Sciences en Auckland Cancer Research en School of Medicine en Obstetrics and Gynaecology en Science en Science Research en Maurice Wilkins Centre (2010-2014) en
pubs.record-created-at-source-date 2010-09-01 en
pubs.dimensions-id 20217871 en

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