Evidence map›Paper›PMID 31028279›Full record

ArticleLaboratory investigation; a journal of technical methods and pathology2019

Mesenchyme-specific deletion of Tgf-β1 in the embryonic lung disrupts branching morphogenesis and induces lung hypoplasia.

Niki Noe, Ashley Shim, Katelyn Millette, Yongfeng Luo, Mohamad Azhar, Wei Shi, David Warburton, Gianluca Turcatel

Open access · greenAbstract read
In one paragraph

Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.7field-weighted citation impact, top 11% of its field
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

21 citing papers in PubMed, 35 citations in OpenAlex.

  1. Trial
  2. Article
  3. Regulation of inflammatory lung injury and repair by transforming growth factors.American journal of physiology. Lung cellular and molecular physiology · 2025
    Review
  4. Article
  5. Article
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  13. Review
  14. Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia.American journal of physiology. Lung cellular and molecular physiology · 2023
    Review
  15. Mechanics of Lung Development.Advances in anatomy, embryology, and cell biology · 2023
    Article
  16. Article
  17. Review
  18. R-SPONDIN2Developmental cell · 2022
    Article
  19. Review
  20. 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

8 authors at 2 institutions in 1 country.

Niki NoeDevelopmental Biology and Regenerative Medicine Program, The Saban Research Institute, Children's Hospital Los Angeles, 4661 Sunset Boulevard, Los Angeles, CA, 90027, USA.
Ashley ShimDevelopmental Biology and Regenerative Medicine Program, The Saban Research Institute, Children's Hospital Los Angeles, 4661 Sunset Boulevard, Los Angeles, CA, 90027, USA.
Katelyn MilletteDevelopmental Biology and Regenerative Medicine Program, The Saban Research Institute, Children's Hospital Los Angeles, 4661 Sunset Boulevard, Los Angeles, CA, 90027, USA.
Yongfeng LuoDevelopmental Biology and Regenerative Medicine Program, The Saban Research Institute, Children's Hospital Los Angeles, 4661 Sunset Boulevard, Los Angeles, CA, 90027, USA.
Mohamad AzharDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC, 29202, USA.
Wei ShiDevelopmental Biology and Regenerative Medicine Program, The Saban Research Institute, Children's Hospital Los Angeles, 4661 Sunset Boulevard, Los Angeles, CA, 90027, USA.
David WarburtonDevelopmental Biology and Regenerative Medicine Program, The Saban Research Institute, Children's Hospital Los Angeles, 4661 Sunset Boulevard, Los Angeles, CA, 90027, USA.
Gianluca TurcatelDevelopmental Biology and Regenerative Medicine Program, The Saban Research Institute, Children's Hospital Los Angeles, 4661 Sunset Boulevard, Los Angeles, CA, 90027, USA. gturcatel@chla.usc.edu.
Children's Hospital of Los Angeles · USUniversity of South Carolina · US

Funding

Molecular anatomy of human alveolar developmentU01HL122681 · NHLBI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI WARBURTON, DAVID · 2014 to 2018
$4.0M
Medial Arterial Calcification: Mechanisms and TherapyR01HL145064 · NHLBI · CLEMSON UNIVERSITY · PI VYAVAHARE, NAREN R · 2019 to 2022
$2.3M
Analysis of TGFbeta ligands function in heart development and diseaseR01HL126705 · NHLBI · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI AZHAR, MOHAMAD · 2015 to 2018
$1.4M
Development of a novel genetic approach to study lung mesenchymal cell signalingR21HL109932 · NHLBI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI SHI, WEI · 2011 to 2012
$440k
NHLBI NIH HHS R01 HL126705NHLBI NIH HHS R01 HL145064NHLBI NIH HHS R21 HL109932NHLBI NIH HHS U01 HL122681
6 · The paper itself

Abstract

Proper lung development depends on the precise temporal and spatial expression of several morphogenic factors, including Fgf10, Fgf9, Shh, Bmp4, and Tgf-β. Over- or under-expression of these molecules often leads to aberrant embryonic or postnatal lung development. Herein, we deleted the Tgf-β1 gene specifically within the lung embryonic mesenchymal compartment at specific gestational stages to determine the contribution of this cytokine to lung development. Mutant embryos developed severe lung hypoplasia and died at birth due to the inability to breathe. Despite the markedly reduced lung size, proliferation and differentiation of the lung epithelium was not affected by the lack of mesenchymal expression of the Tgf-β1 gene, while apoptosis was significantly increased in the mutant lung parenchyma. Lack of mesenchymal expression of the Tgf-β1 gene was also associated with reduced lung branching morphogenesis, with accompanying inhibition of the local FGF10 signaling pathway as well as abnormal development of the vascular system. To shed light on the mechanism of lung hypoplasia, we quantified the phosphorylation of 226 proteins in the mutant E12.5 lung compared with control. We identified five proteins, Hrs, Vav2, c-Kit, the regulatory subunit of Pi3k (P85), and Fgfr1, that were over- or under-phosphorylated in the mutant lung, suggesting that they could be indispensable effectors of the TGF-β signaling program during embryonic lung development. In conclusion, we have uncovered novel roles of the mesenchyme-specific Tgf-β1 ligand in embryonic mouse lung development and generated a mouse model that may prove helpful to identify some of the key pathogenic mechanisms underlying lung hypoplasia in humans.

Indexed as

Transforming Growth Factor beta1AnimalsAnimals, NewbornApoptosisCell Culture TechniquesFemaleGene Knockout TechniquesLungLung DiseasesMaleMesodermMiceMice, TransgenicMorphogenesisTgfb1 protein, mouseTransforming Growth Factor beta1

Identifiers

PMID31028279
PMCPMC7422700
OpenAlexW2941346440

What OpenQuestion holds

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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 OpenQuestion graph.