Evidence map›Paper›PMID 25047515›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2014

Therapeutic targeting of SRC kinase in myofibroblast differentiation and pulmonary fibrosis.

Meng Hu, Pulin Che, Xiaosi Han, Guo-Qiang Cai, Gang Liu, Veena Antony, Tracy Luckhardt, Gene P Siegal, Yong Zhou, Rui-ming Liu and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

69 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
  2. S100A4 Orchestrates Fibroblast Fate to Drive Fibrotic Remodeling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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  4. Emerging Concepts in Therapeutic Interventions for Idiopathic Pulmonary Fibrosis.Seminars in respiratory and critical care medicine · 2025
    Review
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  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Dual Drug Repurposing: The Example of Saracatinib.International journal of molecular sciences · 2024
    Review
  13. Review
  14. Logic-based mechanistic machine learning on high-content images reveals how drugs differentially regulate cardiac fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

9 more citing papers are in PubMed but not listed here.

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

14 authors at 1 institution in 1 country.

Meng HuDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Pulin CheDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Xiaosi HanDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Guo-Qiang CaiDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Gang LiuDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Veena AntonyDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Tracy LuckhardtDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Gene P SiegalDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Yong ZhouDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Rui-ming LiuDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Leena P DesaiDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Philip J O'ReillyDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Victor J ThannickalDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama.
Qiang DingDepartments of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine (M.H., G.Q.-C., G.L., V.A., T.L., Y.Z., R.L., L.P.D., P.J.O., V.J.T., Q.D.), Cell, Development, and Integrative Biology (P.C.), Neurology (X.H.), and Pathology (G.P.S.), University of Alabama at Birmingham, Birmingham, Alabama qding@uab.edu.
University of Alabama at Birmingham · US

Funding

Therapeutic Targeting of the Myofibroblast in Fibrotic Lung DiseaseP01HL114470 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI THANNICKAL, VICTOR J. · 2013 to 2022
$17.8M
The Role of FAK-related-non-kinase (FRNK) in Lung FibrosisR01HL085324 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DING, QIANG · 2007 to 2016
$3.9M
miR-21 and lung fibrosisR01HL105473 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LIU, GANG · 2011 to 2015
$1.8M
Myofibroblast Senescence in Pulmonary FibrosisR01AG046210 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI THANNICKAL, VICTOR J. · 2014 to 2018
$1.6M
NHLBI NIH HHS P01 HL114470NHLBI NIH HHS P01-HL114470NHLBI NIH HHS R01 HL085324NHLBI NIH HHS R01-HL085324NHLBI NIH HHS R01 HL105473NHLBI NIH HHS R01-HL105473NIA NIH HHS R01 AG046210
6 · The paper itself

Abstract

Myofibroblasts are effector cells in fibrotic disorders that synthesize and remodel the extracellular matrix (ECM). This study investigated the role of the Src kinase pathway in myofibroblast activation in vitro and fibrogenesis in vivo. The profibrotic cytokine, transforming growth factor β1 (TGF-β1), induced rapid activation of Src kinase, which led to myofibroblast differentiation of human lung fibroblasts. The Src kinase inhibitor AZD0530 (saracatinib) blocked TGF-β1-induced Src kinase activation in a dose-dependent manner. Inhibition of Src kinase significantly reduced α-smooth muscle actin (α-SMA) expression, a marker of myofibroblast differentiation, in TGF-β1-treated lung fibroblasts. In addition, the induced expression of collagen and fibronectin and three-dimensional collagen gel contraction were also significantly inhibited in AZD0530-treated fibroblasts. The therapeutic efficiency of Src kinase inhibition in vivo was tested in the bleomycin murine lung fibrosis model. Src kinase activation and collagen accumulation were significantly reduced in the lungs of AZD0530-treated mice when compared with controls. Furthermore, the total fibrotic area and expression of α-SMA and ECM proteins were significantly decreased in lungs of AZD0530-treated mice. These results indicate that Src kinase promotes myofibroblast differentiation and activation of lung fibroblasts. Additionally, these studies provide proof-of-concept for targeting the noncanonical TGF-β signaling pathway involving Src kinase as an effective therapeutic strategy for lung fibrosis.

Indexed as

Cell DifferentiationActinsAnimalsBenzodioxolesCell LineCells, CulturedCollagenEnzyme InhibitorsFemaleHumansMaleMiceMice, Inbred C57BLMyofibroblastsPulmonary FibrosisQuinazolinesActinsBenzodioxolesCollagenEnzyme InhibitorsQuinazolinessaracatinibsrc-Family KinasesTransforming Growth Factor beta

Identifiers

PMID25047515
PMCPMC4165028
OpenAlexW2117624308

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.