Evidence map›Paper›PMID 39455836›Full record

ArticleNature cardiovascular research2024

Bone-marrow macrophage-derived GPNMB protein binds to orphan receptor GPR39 and plays a critical role in cardiac repair.

Sivakumar Ramadoss, Juan Qin, Bo Tao, Nathan E Thomas, Edward Cao, Rimao Wu, Daniel R Sandoval, Ann Piermatteo, Kaare V Grunddal, Feiyang Ma and 9 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Novel Roles of GPCRs in the Renal Collecting Duct.Physiology (Bethesda, Md.) · 2026
    Review
  2. Review
  3. Immunometabolic Remodeling in Ischemic and Non-Ischemic Heart Failure.Journal of cardiovascular translational research · 2026
    Review
  4. Article
  5. GPR39-mediated molecular signaling by bile acids.The Journal of biological chemistry · 2026
    Article
  6. Regenerative therapy · 2026
    Article
  7. GPR39 activation inhibits AQP2 trafficking and alters cytoskeletal organization.American journal of physiology. Cell physiology · 2026
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Macrophage GPNMB-mediated cardiac repair.Nature cardiovascular research · 2024
    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

19 authors.

Sivakumar Ramadoss *Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Juan Qin *Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Bo TaoDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Nathan E ThomasDepartment of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, CA, USA.
Edward CaoDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Rimao WuDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Daniel R SandovalDepartment of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, CA, USA.
Ann PiermatteoDepartment of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, CA, USA.
Kaare V GrunddalDepartment of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9352-7220
Feiyang MaDepartment of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-6260-0787
Shen LiDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Baiming SunDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Yonggang ZhouDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Jijun WanDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Matteo PellegriniDepartment of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California-Los Angeles, Los Angeles, CA, USA.
Birgitte HolstDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-7432-097X
Aldons J LusisDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-9013-0228
Philip L S M GordtsDepartment of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, CA, USA.
Arjun DebDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA. adeb@mednet.ucla.edu.ORCID http://orcid.org/0000-0003-0978-2611

Funding

Metabolic and epigenetic reprogramming of vital organs in SARS-CoV-2 induced systemic toxicityR01DK132735 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARUMUGASWAMI, VAITHILINGARAJA, DEB, ARJUN · 2021 to 2023
$6.0M
EXPERIMENTAL ENDOCRINOLOGY AND METABOLISMT32DK007044 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Amit Majithia · 1986 to 2026
$4.6M
Role of GPNMB in cardiac remodelingR01HL152176 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2021 to 2024
$2.8M
Targeting cardiac fibroblast-myocyte cross talk to enhance heart function after cardiac injuryR01HL149658 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2020 to 2023
$2.2M
Role of collagen heterogeneity in remodeling of acute and chronic heart scarsR01HL149687 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN, PELLEGRINI, MATTEO · 2020 to 2023
$2.0M
National Heart and Lung Institute (NHLI) HL149658NHLBI NIH HHS R01 HL149658NHLBI NIH HHS R01 HL149687NHLBI NIH HHS R01 HL152176NIDDK NIH HHS R01 DK132735NIDDK NIH HHS T32 DK007044
6 · The paper itself

Abstract

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein initially identified in nonmetastatic melanomas and has been associated with human heart failure; however, its role in cardiac injury and function remains unclear. Here we show that GPNMB expression is elevated in failing human and mouse hearts after myocardial infarction (MI). Lineage tracing and bone-marrow transplantation reveal that bone-marrow-derived macrophages are the main source of GPNMB in injured hearts. Using genetic loss-of-function models, we demonstrate that GPNMB deficiency leads to increased mortality, cardiac rupture and rapid post-MI left ventricular dysfunction. Conversely, increasing circulating GPNMB levels through viral delivery improves heart function after MI. Single-cell transcriptomics show that GPNMB enhances myocyte contraction and reduces fibroblast activation. Additionally, we identified GPR39 as a receptor for circulating GPNMB, with its absence negating the beneficial effects. These findings highlight a pivotal role of macrophage-derived GPNMBs in post-MI cardiac repair through GPR39 signaling.

Indexed as

Disease Models, AnimalMacrophagesMembrane GlycoproteinsMice, KnockoutMyocardial InfarctionMyocytes, CardiacReceptors, G-Protein-CoupledAnimalsBone Marrow TransplantationCells, CulturedEye ProteinsFemaleHeart FailureHumansMaleMiceEye ProteinsGPNMB protein, humanGpnmb protein, mouseMembrane GlycoproteinsReceptors, G-Protein-Coupled

Identifiers

PMID39455836

What OpenQuestion holds

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Read underepoch 390

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 OpenQuestion graph.