Evidence map›Paper›PMID 41820365›Full record

ArticleNature communications2026

Megakaryocyte and platelet thrombospondin-1 regulates matrix remodeling by stabilizing basement membrane COL6A1 in lung injury.

Hernán F Peñaloza, Atish Gheware, Ananya Gupta, Donovan Watza, Anupam Kumari, Shekina Gonzalez-Ferrer, Zeyu Xiong, Xingan Wang, Gregory Gibson, Pooja Bhojraj and 21 more

Abstract read
In one paragraph

Article in Nature communications, 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. Review
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

31 authors.

Hernán F Peñaloza *Acute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-1593-678X
Atish Gheware *Acute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Ananya GuptaDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-7917-7877
Donovan WatzaDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-6882-065X
Anupam KumariDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Shekina Gonzalez-FerrerAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Zeyu XiongAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Xingan WangAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Gregory GibsonCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, USA.
Pooja BhojrajDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Rick van der GeestAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-1973-5934
Jae-Sung KimDepartment of Medicine, Division of Hematology, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0009-0007-0378-345X
Bo-Ram JinDepartment of Medicine, Division of Hematology, Washington University in St. Louis, St. Louis, MO, USA.
Mélia MagnenDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5189-0072
William G BainAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-8506-0552
Mohammadreza TabaryAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Liwen ZhangMass Spectrometry and Proteomics Facility, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0003-1696-9652
Arpad SomogyMass Spectrometry and Proteomics Facility, The Ohio State University, Columbus, OH, USA.
Tomasz KaminskiThrombosis and Hemostasis Program, VERSITI Blood Research Institute, Milwaukee, WI, USA.ORCID http://orcid.org/0000-0002-8688-4171
Prithu SunddThrombosis and Hemostasis Program, VERSITI Blood Research Institute, Milwaukee, WI, USA.ORCID http://orcid.org/0000-0001-7568-5719
Kyunghee ChoiDepartment of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9634-9375
Anuradha RayAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-6844-8918
Prabir RayAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-0430-5114
Rama K MallampalliDepartment of Medicine, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0002-5782-4495
Sebastien GingrasDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-2607-8642
Matthew R RosengartDepartment of Surgery, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-9203-5478
Mark R LooneyDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0241-9190
Jonathan K AlderAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-3741-6512
Jaehyung ChoDepartment of Medicine, Division of Hematology, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-2404-3446
Claudette St CroixCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, USA.
Janet S LeeAcute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA. ljanet@wustl.edu.ORCID http://orcid.org/0000-0002-6812-6043

Funding

Regulation of Cardiolin Byosynthesis in Epithelial InjuryP01HL114453 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2014 to 2023
$21.3M
Pulmonary arteriole occlusion by platelet-neutrophil micro-emboli in Acute Chest SyndromeR01HL128297 · NHLBI · VERSITI WISCONSIN, INC. · PI SUNDD, PRITHU · 2015 to 2025
$5.4M
Mechanisms of host protection against pathogen-secreted proteases in acute lung injuryR01HL136143 · NHLBI · WASHINGTON UNIVERSITY · PI LEE, JANET SOJUNG · 2017 to 2024
$4.4M
Immunobiology of the normal and injured lungR35HL161241 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARK ROBERTS LOONEY · 2022 to 2026
$4.2M
Thiol isomerases in neutrophil recruitment and thromboinflammatory diseaseR01HL130028 · NHLBI · WASHINGTON UNIVERSITY · PI CHO, JAEHYUNG · 2016 to 2024
$3.6M
Immunomodulation by splenic megakaryocytes and platelets in sepsisR01AI165919 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOONEY, MARK ROBERTS · 2022 to 2025
$3.2M
The role of ACOD1 in immunomodulation in intrapulmonary Klebsiella pneumoniae infectionR01HL142084 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, KONG · 2018 to 2021
$2.4M
Ero1α in platelet activity and thrombosisR01HL146559 · NHLBI · WASHINGTON UNIVERSITY · PI CHO, JAEHYUNG · 2020 to 2023
$1.7M
Role of intravascular ERO1@ in acute lung injuryR01HL153047 · NHLBI · WASHINGTON UNIVERSITY · PI CHO, JAEHYUNG · 2020 to 2023
$1.6M
Spatiotemporal control of early matricellular events in the injured lungR01HL177904 · NHLBI · WASHINGTON UNIVERSITY · PI Jaehyung Cho, Janet Sojung Lee · 2025 to 2026
$1.5M
Mechanisms regulating neutrophil proinflammatory activity in sepsisR01AI181792 · NIAID · WASHINGTON UNIVERSITY · PI Jaehyung Cho · 2025 to 2026
$1.0M
Patient-Oriented Research in Acute Lung Injury and Host Defense in the ICUK24HL143285 · NHLBI · WASHINGTON UNIVERSITY · PI LEE, JANET SOJUNG · 2019 to 2023
$579k
NHLBI NIH HHS K24 HL143285NHLBI NIH HHS P01 HL114453NHLBI NIH HHS R01 HL128297NHLBI NIH HHS R01 HL130028NHLBI NIH HHS R01 HL136143NHLBI NIH HHS R01 HL142084NHLBI NIH HHS R01 HL146559NHLBI NIH HHS R01 HL153047NHLBI NIH HHS R01 HL177904NHLBI NIH HHS R35 HL161241NIAID NIH HHS R01 AI165919NIAID NIH HHS R01 AI181792U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL142084U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01 K24 HL14285
6 · The paper itself

Abstract

An early event after lung injury is extracellular matrix (ECM) remodeling and the formation of a provisional matrix. While megakaryocytes and platelets (Mgk/plt) play important roles in hemostasis, their impact on the matrix in lung injury is not fully understood. Using lung intravital microscopy, 3D large area scanning with multiphoton confocal hybrid imaging, and label-free quantitative proteomics, the matricellular protein thrombospondin-1 (TSP1) arising from Mgk/plt protects the lung from alveolar injury. Mgk/plt cell-specific Thbs1 knockout (cKO) mice show increased alveolar barrier disruption with exaggerated neutrophil-mediated injury. The cKO mice exhibit striking extracellular matrix re-organization with reduction in basement membrane matrix protein COL6A1 after injury. Moreover, cKO mice increase Mgk numbers to regions of fibrillar collagen deposition and alveolar leak. Our findings indicate Mgk/plt-derived TSP1 represents a key mechanism of matrix stabilization by protecting the basement membrane from neutrophil-mediated proteolytic damage, regulating injury severity and Mgk numbers at the alveolar interface.

Indexed as

Basement MembraneBlood PlateletsExtracellular MatrixLung InjuryMegakaryocytesThrombospondin 1AnimalsLungMaleMiceMice, Inbred C57BLMice, KnockoutNeutrophilsThbs1 protein, mouseThrombospondin 1

Identifiers

PMID41820365
PMCPMC13121761

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.