Evidence map›Paper›PMID 41564150›Full record

ArticleHypertension (Dallas, Tex. : 1979)2026

BMP9 Modulates IL-33 Signaling to Mitigate EndMT in Pulmonary Arterial Hypertension.

Clarissa Becher, Esmee J Groeneveld, Rozenn Quarck, Beau Neep, Xiaoke Pan, Robert Szulcek, Ly Tu, Christophe Guignabert, Harm Jan Bogaard, Paul B Yu and 3 more

Abstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

13 authors.

Clarissa BecherDepartment of Cell and Chemical Biology, Leiden University Medical Center, the Netherlands (C.B., E.J.G., R.S., G.S.-D., M.-J.G.).ORCID 0000-0002-1811-8037
Esmee J GroeneveldDepartment of Cell and Chemical Biology, Leiden University Medical Center, the Netherlands (C.B., E.J.G., R.S., G.S.-D., M.-J.G.).ORCID 0000-0001-6730-1498
Rozenn QuarckDepartment of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery, KU Leuven-University of Leuven, Belgium (R.Q.).ORCID 0000-0002-8293-6261
Beau NeepDepartment of Pulmonary Medicine, PHEniX Laboratory, Amsterdam University Medical Center (Vrije Universiteit), The Netherlands (B.N., X.P., R.S., H.J.B., F.d.M.).ORCID 0009-0008-3968-9569
Xiaoke PanDepartment of Pulmonary Medicine, PHEniX Laboratory, Amsterdam University Medical Center (Vrije Universiteit), The Netherlands (B.N., X.P., R.S., H.J.B., F.d.M.).ORCID 0009-0004-0251-1979
Robert SzulcekDepartment of Cell and Chemical Biology, Leiden University Medical Center, the Netherlands (C.B., E.J.G., R.S., G.S.-D., M.-J.G.).ORCID 0000-0003-0450-7338
Ly TuFaculté de Médecine, Hypertension Pulmonaire: Physiopathology and Innovation Thérapeutique, Université Paris-Saclay, Le Kremlin-Bicêtre, France (L.T., C.G.).
Christophe GuignabertFaculté de Médecine, Hypertension Pulmonaire: Physiopathology and Innovation Thérapeutique, Université Paris-Saclay, Le Kremlin-Bicêtre, France (L.T., C.G.).ORCID 0000-0002-8545-4452
Harm Jan BogaardDepartment of Pulmonary Medicine, PHEniX Laboratory, Amsterdam University Medical Center (Vrije Universiteit), The Netherlands (B.N., X.P., R.S., H.J.B., F.d.M.).ORCID 0000-0001-5371-0346
Paul B YuDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (P.B.Y.).ORCID 0000-0003-2145-4944
Frances de ManDepartment of Pulmonary Medicine, PHEniX Laboratory, Amsterdam University Medical Center (Vrije Universiteit), The Netherlands (B.N., X.P., R.S., H.J.B., F.d.M.).ORCID 0000-0002-5776-7793
Gonzalo Sanchez-Duffhues *Department of Cell and Chemical Biology, Leiden University Medical Center, the Netherlands (C.B., E.J.G., R.S., G.S.-D., M.-J.G.).ORCID 0000-0002-3205-0710
Marie-José Goumans *Department of Cell and Chemical Biology, Leiden University Medical Center, the Netherlands (C.B., E.J.G., R.S., G.S.-D., M.-J.G.).ORCID 0000-0001-9344-6746

Funding

Context-specific angiogenic signaling in the pulmonary vasculatureR01HL159443 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI YU, PAUL B · 2021 to 2024
$2.4M
NHLBI NIH HHS R01 HL159443
6 · The paper itself

Abstract

backgroundPulmonary arterial hypertension (PAH) is a progressive disorder involving disrupted BMP (bone morphogenetic protein) signaling, pulmonary inflammation, and endothelial-to-mesenchymal transition (EndMT). We hypothesized that IL (interleukin)-33 signaling contributes to PAH progression by inducing EndMT and interacting with BMP9, a key modulator of inflammation and vascular remodeling.

methodsIL-33 expression was assessed in lung tissues from Sugen/hypoxia and control mice, as well as in pulmonary arterial endothelial cells (PAECs) and lung tissues from patients with PAH and healthy donors. EndMT and signaling pathways were analyzed in PAECs and microvascular endothelial cells (MVECs) exposed to IL-33, BMP9, and sST2 (soluble supression of tumorigenicity 2) using quantitative polymerase chain reaction, Western blotting, ELISA, and immunostaining. Plasma BMP9 and sST2 levels were quantified in patients with PAH.

resultsImmunofluorescent analysis revealed elevated IL-33 expression in pulmonary endothelial cells of Sugen/hypoxia mice compared with controls, consistent with findings in PAECs from patients with PAH. BMP9 significantly upregulated sST2 expression in human PAEC and microvascular endothelial cells, inhibited IL-33 target gene expression, and effectively suppressed IL-33-induced EndMT. Notably, BMP9 demonstrated greater efficacy in preventing EndMT compared with rsST2 (recombinant soluble ST2) or ST2L-neutralizing antibodies. Circulating BMP9 and sST2 levels in the plasma of patients with PAH were positively correlated in specific patient groups stratified by sex, age, and New York Heart Association functional class, suggesting a protective role of BMP9 in modulating IL-33-induced EndMT.

conclusionsBMP9 plays a protective role against IL-33-induced EndMT in PAECs by upregulating sST2 expression and neutralizing IL-33, suggesting that targeting the IL-33 signaling pathway may represent a promising therapeutic strategy to mitigate EndMT in PAH.

Indexed as

Endothelial-Mesenchymal TransitionGrowth Differentiation Factor 2Hypertension, PulmonaryInterleukin-33Pulmonary Arterial HypertensionAnimalsCells, CulturedDisease Models, AnimalEndothelial CellsFemaleHumansInterleukin-1 Receptor-Like 1 ProteinMaleMiceSignal TransductionVascular RemodelingGDF2 protein, humanGrowth Differentiation Factor 2IL33 protein, humanInterleukin-1 Receptor-Like 1 ProteinInterleukin-33bone morphogenetic proteinscytokinesdisease models, animalendothelial cellspulmonary arterial hypertension

Identifiers

PMID41564150
PMCPMC12822782

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

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 Socratic graph.