A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia.

Ghorbanpour, SM; Richards, C; Pienaar, D; Sesperez, K; Aboulkheyr Es, H; Nikolic, VN; Karadzov Orlic, N; Mikovic, Z; Stefanovic, M; Cakic, Z; Alqudah, A; Cole, L; Gorrie, C; McGrath, K; Kavurma, MM; Ebrahimi Warkiani, M; McClements, L

A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia.

Ghorbanpour, SM Richards, C

Pienaar, D Sesperez, K Aboulkheyr Es, H Nikolic, VN Karadzov Orlic, N Mikovic, Z Stefanovic, M Cakic, Z Alqudah, A Cole, L

Gorrie, C

McGrath, K

Kavurma, MM Ebrahimi Warkiani, M McClements, L

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Publisher:: SPRINGER BASEL AG
Publication Type:: Journal Article
Citation:: Cell Mol Life Sci, 2023, 80, (2), pp. 44
Issue Date:: 2023-01-18

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Field	Value	Language
dc.contributor.author	Ghorbanpour, SM
dc.contributor.author	Richards, C https://orcid.org/0000-0001-5080-9164
dc.contributor.author	Pienaar, D
dc.contributor.author	Sesperez, K
dc.contributor.author	Aboulkheyr Es, H
dc.contributor.author	Nikolic, VN
dc.contributor.author	Karadzov Orlic, N
dc.contributor.author	Mikovic, Z
dc.contributor.author	Stefanovic, M
dc.contributor.author	Cakic, Z
dc.contributor.author	Alqudah, A
dc.contributor.author	Cole, L https://orcid.org/0000-0001-9206-9272
dc.contributor.author	Gorrie, C https://orcid.org/0000-0001-5934-2492
dc.contributor.author	McGrath, K https://orcid.org/0000-0002-6244-3929
dc.contributor.author	Kavurma, MM
dc.contributor.author	Ebrahimi Warkiani, M
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.date.accessioned	2024-01-11T04:48:48Z
dc.date.available	2022-11-24
dc.date.available	2024-01-11T04:48:48Z
dc.date.issued	2023-01-18
dc.identifier.citation	Cell Mol Life Sci, 2023, 80, (2), pp. 44
dc.identifier.issn	1420-682X
dc.identifier.issn	1420-9071
dc.identifier.uri	http://hdl.handle.net/10453/174313
dc.description.abstract	Preeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsia and normotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-α (10 ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia.
dc.format	Electronic
dc.language	eng
dc.publisher	SPRINGER BASEL AG
dc.relation.ispartof	Cell Mol Life Sci
dc.relation.isbasedon	10.1007/s00018-022-04648-w
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 0606 Physiology, 1103 Clinical Sciences
dc.subject.classification	Biochemistry & Molecular Biology
dc.subject.classification	3101 Biochemistry and cell biology
dc.subject.classification	3205 Medical biochemistry and metabolomics
dc.subject.classification	3211 Oncology and carcinogenesis
dc.subject.mesh	Pregnancy
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Placenta
dc.subject.mesh	Galectin 3
dc.subject.mesh	Pre-Eclampsia
dc.subject.mesh	Trophoblasts
dc.subject.mesh	Human Umbilical Vein Endothelial Cells
dc.subject.mesh	Cell Cycle Proteins
dc.subject.mesh	Lab-On-A-Chip Devices
dc.subject.mesh	Tacrolimus Binding Proteins
dc.subject.mesh	Trophoblasts
dc.subject.mesh	Placenta
dc.subject.mesh	Humans
dc.subject.mesh	Pre-Eclampsia
dc.subject.mesh	Tacrolimus Binding Proteins
dc.subject.mesh	Cell Cycle Proteins
dc.subject.mesh	Galectin 3
dc.subject.mesh	Pregnancy
dc.subject.mesh	Female
dc.subject.mesh	Lab-On-A-Chip Devices
dc.subject.mesh	Human Umbilical Vein Endothelial Cells
dc.subject.mesh	Pregnancy
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Placenta
dc.subject.mesh	Galectin 3
dc.subject.mesh	Pre-Eclampsia
dc.subject.mesh	Trophoblasts
dc.subject.mesh	Human Umbilical Vein Endothelial Cells
dc.subject.mesh	Cell Cycle Proteins
dc.subject.mesh	Lab-On-A-Chip Devices
dc.subject.mesh	Tacrolimus Binding Proteins
dc.title	A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia.
dc.type	Journal Article
utslib.citation.volume	80
utslib.location.activity	Switzerland
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	0606 Physiology
utslib.for	1103 Clinical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2024-01-11T04:48:34Z
pubs.issue	2
pubs.publication-status	Published online
pubs.volume	80
utslib.citation.issue	2

Abstract:

Preeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsia and normotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-α (10 ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia.

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http://hdl.handle.net/10453/174313