Evidence map›Paper›PMID 40502186›Full record

ArticlebioRxiv : the preprint server for biology2025

VGLL3-centered network connects placental, vascular, and immune defects in preeclampsia.

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

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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 PlazyoDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-6859-7590
Laura B ChoppDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Rishyanth PeelaDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Kelly YoungDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Haihan ZhangDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Rachael BogleDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Ashley HessonDepartment of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA.
Elizabeth S LangenDepartment of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA.
Ingrid L BerginUnit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Li-Jyun SyuDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Jake ErbaDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Joseph KirmaDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Poulami DeyDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Lin ZhangDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Mrinal K SarkarDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
William R SwindellDepartment of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Katherine A GallagherDepartment of Surgery, Division of Vascular Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Nicole L WardDepartment of Dermatology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Kanakadurga SingerDivision of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
J Michelle KahlenbergDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Allison C BilliDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Andrzej A DlugoszDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Santhi K GaneshDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Lam C TsoiDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Johann E GudjonssonDepartment of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.

Funding

University of Michigan Skin Biology and Diseases Resource-based CenterP30AR075043 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANDRZEJ A. DLUGOSZ · 2019 to 2026
$6.6M
Kallikrein-PAR interactions in skin inflammationR01AR073196 · NIAMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WARD, NICOLE LEANNE · 2018 to 2023
$3.3M
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
Linking Disease Mechanisms and Outcomes in Rheumatic DiseasesK24AR076975 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joanne Michelle Kahlenberg · 2020 to 2026
$910k
Mechanisms of sex discrepancy in autoimmune disease: Regulation of the female-biased VGLL3 immune pathwayK08AR078251 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BILLI, ALLISON CHELSA · 2021 to 2025
$865k
NIAID NIH HHS R01 AI183620NIAMS NIH HHS K08 AR078251NIAMS NIH HHS K24 AR076975NIAMS NIH HHS P30 AR075043NIAMS NIH HHS R01 AR073196
6 · The paper itself

Abstract

Preeclampsia 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. Through human single-cell and spatial analyses, coupled with in vitro, in vivo, and ex vivo models, we demonstrate that VGLL3, a transcription co-regulator in the Hippo pathway, is upregulated in preeclamptic placentas. VGLL3 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, 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. These findings position VGLL3 as a promising novel therapeutic target for preeclampsia.

Identifiers

PMID40502186
PMCPMC12157399

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.