ADAM8 localizes to extravillous trophoblasts within the maternal–fetal interface and potentiates trophoblast cell line migration through a β1 integrin-mediated mechanism

Le, Hoa; Atif, Jawairia; Mara, Danielle L.; Castellana, Bàrbara; Treissman, Jenna; Baltayeva, Jennet; Beristain, Alexander G.

doi:10.1093/molehr/gay034

Cited by 15 publications

(13 citation statements)

References 41 publications

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“…For instance, the α5 subunit colocalizes and interacts with pregnancy-specific glycoprotein-1 to promote the adhesion of the EVTs to the decidual cells [28]. On the other hand, the β1 subunit associates with A disintegrin and metalloproteinase domain-8 (ADAM8) during the initial stages of cell-matrix attachment, suggesting that ADAM8 may enhance β1 subcellular localization to actin-rich structures or may regulate the configuration of β1 [29]. N-glycosylation of β1 modulates the functions of β1 [23].…”

Section: Integrinsmentioning

confidence: 99%

The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation

et al. 2020

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Placentation is a major determinant of the success of pregnancy. It is regulated by several factors such as cell adhesion molecules, tight junctions, and gap junctions. The cell adhesion molecules are integrins, cadherins, immunoglobulins, nectins, and selectins. The tight junctions are composed of claudins, occludin, and junction adhesion molecule proteins while the gap junctions are composed of connexins of varying molecular weights. During placentation, some of these molecules regulate trophoblast proliferation, trophoblast fusion, trophoblast migration, trophoblast invasion, trophoblastendothelium adhesion, glandular remodeling, and spiral artery remodeling. There is a dysregulated placental expression of some of these molecules during obstetric complications. We have, hereby, indicated the expression patterns of the subunits of each of these molecules in the various trophoblast subtypes and in the decidua, and have highlighted their involvement in physiological and pathological placentation. The available evidence points to the relevance of these molecules as distinguishing markers of the various trophoblast lineages and as potential therapeutic targets in the management of malplacentation-mediated diseases.

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Section: Integrinsmentioning

confidence: 99%

The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation

et al. 2020

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“…EVTs play a very important role in the development of the placenta [ 46 , 47 ]. They migrate and invade spiral arteries, which is critical for remodeling [ 46 , 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function

Ashar

Teng²,

Wurpel³

et al. 2022

Biomolecules

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Normal function of placental extravillous trophoblasts (EVTs), which are responsible for uteroplacental vascular remodeling, is critical for adequate delivery of oxygen and nutrients to the developing fetus and normal fetal programming. Proliferation and invasion of spiral arteries by EVTs depends upon adequate levels of folate. Multidrug resistance-associated protein 1 (MRP1), which is an efflux transporter, is known to remove folate from these cells. We hypothesized that palmitic acid increases MRP1-mediated folate removal from EVTs, thereby interfering with EVTs’ role in early placental vascular remodeling. HTR-8/SVneo and Swan-71 cells, first trimester human EVTs, were grown in the absence or presence of 0.5 mM and 0.7 mM palmitic acid, respectively, for 72 h. Palmitic acid increased ABCC1 gene expression and MRP1 protein expression in both cell lines. The rate of folate efflux from the cells into the media increased with a decrease in migration and invasion functions in the cultured cells. Treatment with N-acetylcysteine (NAC) prevented the palmitic acid-mediated upregulation of MRP1 and restored invasion and migration in the EVTs. Finally, in an ABCC1 knockout subline of Swan-71 cells, there was a significant increase in invasion and migration functions. The novel finding in this study that palmitic acid increases MRP1-mediated folate efflux provides a missing link that helps to explain how maternal consumption of saturated fatty acids compromises the in utero environment.

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“…Previous studies have explored the roles of metzincin proteases in trophoblast biology and have spatially defined MMP2 [19,47], MMP3 [48], MMP14 [49], MMP15 [50], ADAM8 [51], ADAM12 [20][21][22], ADAM28 [52], PAPPA [53], and PAPPA2 [54] to subtypes of trophoblast within first trimester chorionic villi. Single cell transcriptomic assessment of these aforementioned metzincins performed in this study overall supports the conclusions of their previous spatial characterizations, with the majority of these proteases localizing to column trophoblasts and invasive EVT.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic mapping of the metzincin landscape in human trophoblasts

Wächter

Shannon

Castellana

et al. 2022

Preprint

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The metzincin family of metalloproteases coordinates cell and tissue developmental processes through regulation of growth factor availability, receptor signaling, and cell-cell/cell-matrix adhesion. During placental development, while distinct roles for metzincin proteases in controlling specific trophoblast functions have been described, a comprehensive assessment of metzincins during discrete stages of trophoblast differentiation has yet to be performed. Here we provide a comprehensive single cell transcriptomic resource of metzincin protease expression in diverse states of human trophoblasts from first trimester placental and decidual tissues. In the 8 distinct trophoblasts states categorized [four progenitor cytotrophoblast (CTB), one syncytiotrophoblast precursor (SCTp), two column CTB (cCTB), and one extravillous trophoblast (EVT) state], we identified 24 metzincin genes. These included 12 adamalysins, 2 pappalysins, 3 astacins and 7 matrixins. Cell trajectory modeling shows that expression of most (19/24) metzincins increases across CTB to EVT differentiation, though select proteases also increase as CTB fuse into syncytiotrophoblast. Within the CTB niche, single-cell velocity ordering identified 11 metzincins (ADAM10, -17, MMP14, -15, -19, -23B, ADAMTS1, -6, -19, TLL-1, -2) expressed in progenitors proximal to the predicted origin. Analysis of metzincin-substrate interactions within the CTB niche revealed ~150 substrates and binding partners, including FBN2 as an ADAMTS6-specific substrate preferentially expressed in trophoblast progenitors. Together, this work characterizes the metzincin transcriptomic landscape in human first trimester trophoblasts and establishes insight into the roles specific proteases perform within distinct trophoblast niches and across differentiation. This resource serves as a guide for future investigations into the roles of metzincin proteases in human placental development.

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ADAM8 localizes to extravillous trophoblasts within the maternal–fetal interface and potentiates trophoblast cell line migration through a β1 integrin-mediated mechanism

Abstract: NA.

Cited by 15 publications

References 41 publications

The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation

The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation

RETRACTED: Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function

Transcriptomic mapping of the metzincin landscape in human trophoblasts

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