Evidence map›Paper›PMID 41953989›Full record

ArticleCirculation2026

Defective Trophoblast Differentiation, Endothelial Dysfunction, and Immune Dysregulation in Preeclampsia Coalesce on a Placental VGLL3-Centered Gene Network.

Olesya Plazyo, Laura B Chopp, Rishyanth Peela, Kelly Young, Haihan Zhang, Rachael Bogle, Ashley Hesson, Elizabeth S Langen, Ingrid L Bergin, Li-Jyun Syu and 15 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Olesya PlazyoDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0002-6859-7590
Laura B ChoppDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0001-6494-4439
Rishyanth PeelaDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.
Kelly YoungDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.
Haihan ZhangDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0002-5902-7289
Rachael BogleDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0003-3544-3023
Ashley HessonObstetrics(and)Gynecology (A.H., E.S.L.), University of Michigan, Ann Arbor, MI.ORCID 0000-0001-6023-8457
Elizabeth S LangenObstetrics(and)Gynecology (A.H., E.S.L.), University of Michigan, Ann Arbor, MI.ORCID 0000-0002-0169-437X
Ingrid L BerginUnit for Laboratory Animal Medicine (I.L.B.), University of Michigan, Ann Arbor, MI.ORCID 0000-0001-5436-4633
Li-Jyun SyuDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.
Jake ErbaDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.
Joseph KirmaDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.
Poulami DeyDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0001-7589-0034
Lin ZhangDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.
Mrinal K SarkarDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0001-8505-4259
William R SwindellDepartment of Internal Medicine, UT Southwestern Medical Center, Dallas, TX (W.R.S.).
Katherine A GallagherSurgery (K.A.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0002-8791-6980
Nicole L WardDepartment of Dermatology, Vanderbilt University Medical Center, Nashville, TN (N.L.W.).ORCID 0000-0003-1907-2621
Kanakadurga SingerPediatrics (K.S.), University of Michigan, Ann Arbor, MI.ORCID 0000-0001-8278-3800
J Michelle KahlenbergDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0002-4006-8945
Allison C BilliDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0001-7115-9113
Andrzej A DlugoszDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0002-9791-3257
Santhi K GaneshInternal Medicine (J.M.K., S.K.G., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0002-3663-5249
Lam C TsoiDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.
Johann E GudjonssonDepartments of Dermatology (O.P., L.B.C., R.P., K.Y., H.Z., R.B., L.-J.S., J.E., J.K., P.D., L.Z., M.K.S., J.M.K., A.C.B., A.A.D., L.C.T., J.E.G.), University of Michigan, Ann Arbor, MI.ORCID 0000-0002-0080-0812

Funding

Role of the sex biased transcription factor VGLL3 in promoting autoimmune responses in SLER01AI130025 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Johann Eli Gudjonsson · 2017 to 2026
$3.9M
Role of the Hippo pathway in scleroderma pathogenesisR01AI183620 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Johann Eli Gudjonsson, DINESH KHANNA · 2024 to 2026
$1.8M
NIAID NIH HHS R01 AI130025NIAID NIH HHS R01 AI183620
6 · The paper itself

Abstract

backgroundPreeclampsia affects approximately 1 in 10 pregnancies, leading to severe complications and long-term health risks for both mother and offspring. While the etiology remains unclear, preeclampsia has been linked to both autoimmunity and the timing of menarche.

methodsThrough human single-cell and spatial analyses, coupled with in vitro, in vivo, and ex vivo models, we demonstrate that VGLL3 (Vestigial-like family member 3), a transcription coregulator in the Hippo pathway, is upregulated in preeclamptic placentas.

resultsVGLL3 promotes immune activation, impairs trophoblast differentiation, and induces endothelial dysfunction, all of which contribute to pregnancy-related hypertension, fetal growth restriction, and offspring mortality. Our data reveal that VGLL3 acts upstream of preeclampsia-associated processes, including the production of sFLT1 (soluble fms-like tyrosine kinase 1), a key biomarker of the disease. Notably, targeting VGLL3, either by genetic deletion in mouse placentas or through therapeutic inhibition in human placentas, protects against preeclampsia and alleviates disease pathology.

conclusionsThese findings position VGLL3 as a promising novel therapeutic target for preeclampsia.

Indexed as

Cell DifferentiationEndothelium, VascularPlacentaPre-EclampsiaTranscription FactorsTrophoblastsAnimalsFemaleHumansMicePregnancyTranscription Factorsendothelium, vasculargenes, regulatorHippo signaling pathwayhypertension, pregnancy inducedimmunity, activepre-eclampsiatrophoblasts

Identifiers

PMID41953989
PMCPMC13120743

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