MMP-14 is expressed in preeclamptic placentas and mediates release of soluble endoglin

Tu'uhevaha Joy Kaitu'u-Lino, Kirsten Palmer, Clare Whitehead, Elizabeth Williams, Martha Lappas, Stephen Tong

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55 Citations (Scopus)

Abstract

Soluble endoglin is an anti-angiogenic protein that is released from the placenta and contributes to both maternal endothelial dysfunction and the clinical features of severe preeclampsia. The mechanism through which soluble endoglin is released from the placenta is currently unknown; however, recent work in colorectal cancer identified matrix metalloproteinase 14 (MMP-14) as the cleavage protease of endoglin. To determine whether this is also the mechanism responsible for soluble endoglin release in preeclampsia, we investigated the expression of MMP-14 within the placenta and the effects of its inhibition on soluble endoglin release. Placentas were obtained from severe, early onset preeclamptic pregnancies (n = 8) and gestationally matched preterm controls (n = 8). MMP-14 was predominately localized to the syncytiotrophoblast. Results from a proximity ligation assay showed protein interactions between endogenous MMP-14 and endoglin within the preeclamptic placenta. To demonstrate that this interaction produces soluble endoglin, we treated trophoblastic BeWo cells with either a broad-spectrum MMP inhibitor (GM6001) or MMP-14 siRNA. Both treatments produced a decrease in soluble endoglin (P
Original languageEnglish
Pages (from-to)888 - 894
Number of pages7
JournalAmerican Journal of Pathology
Volume180
Issue number3
DOIs
Publication statusPublished - 2012

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