MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.
Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal or...
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doaj-03cd0d9b2df94a4e9785511c6cc51e642020-11-25T00:44:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3986410.1371/journal.pone.0039864MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.Tu'uhevaha J Kaitu'u-LinoKirsten PalmerLaura TuoheyLouie YeStephen TongPreeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15--phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity--also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03) up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8) compared to gestationally matched preterm controls (n = 8). However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.http://europepmc.org/articles/PMC3387233?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tu'uhevaha J Kaitu'u-Lino Kirsten Palmer Laura Tuohey Louie Ye Stephen Tong |
spellingShingle |
Tu'uhevaha J Kaitu'u-Lino Kirsten Palmer Laura Tuohey Louie Ye Stephen Tong MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin. PLoS ONE |
author_facet |
Tu'uhevaha J Kaitu'u-Lino Kirsten Palmer Laura Tuohey Louie Ye Stephen Tong |
author_sort |
Tu'uhevaha J Kaitu'u-Lino |
title |
MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin. |
title_short |
MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin. |
title_full |
MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin. |
title_fullStr |
MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin. |
title_full_unstemmed |
MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin. |
title_sort |
mmp-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15--phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity--also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03) up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8) compared to gestationally matched preterm controls (n = 8). However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin. |
url |
http://europepmc.org/articles/PMC3387233?pdf=render |
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