Evidence map›Paper›PMID 33662577›Full record

ArticleThe international journal of biochemistry & cell biology2021

Selective deletion of connective tissue growth factor attenuates experimentally-induced pulmonary fibrosis and pulmonary arterial hypertension.

Angela Y Y Tam, Amy L Horwell, Sarah L Trinder, Korsa Khan, Shiwen Xu, Voon Ong, Christopher P Denton, Jill T Norman, Alan M Holmes, George Bou-Gharios and 1 more

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

Article in The international journal of biochemistry & cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

19 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Emerging Concepts in Therapeutic Interventions for Idiopathic Pulmonary Fibrosis.Seminars in respiratory and critical care medicine · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Drugs targeting CTGF in the treatment of pulmonary fibrosis.Journal of cellular and molecular medicine · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. The matricellular protein CCN3 supports lung endothelial homeostasis and function.American journal of physiology. Lung cellular and molecular physiology · 2023
    Article
  16. Article
  17. Review
  18. Review
  19. 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

11 authors at 3 institutions in 1 country.

Angela Y Y TamCentre for Rheumatology and Connective Tissue Disease, Department of Inflammation, Division of Medicine, University College London, London, NW3 2PF, UK. Electronic address: angela.tam@ucl.ac.uk.
Amy L HorwellDepartment of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, L7 8TX, UK.
Sarah L TrinderCentre for Rheumatology and Connective Tissue Disease, Department of Inflammation, Division of Medicine, University College London, London, NW3 2PF, UK.
Korsa KhanCentre for Rheumatology and Connective Tissue Disease, Department of Inflammation, Division of Medicine, University College London, London, NW3 2PF, UK.
Shiwen XuCentre for Rheumatology and Connective Tissue Disease, Department of Inflammation, Division of Medicine, University College London, London, NW3 2PF, UK.
Voon OngCentre for Rheumatology and Connective Tissue Disease, Department of Inflammation, Division of Medicine, University College London, London, NW3 2PF, UK.
Christopher P DentonCentre for Rheumatology and Connective Tissue Disease, Department of Inflammation, Division of Medicine, University College London, London, NW3 2PF, UK.
Jill T NormanDepartment of Renal Medicine, Division of Medicine, University College London, London, NW3 2PF, UK.
Alan M HolmesCentre for Rheumatology and Connective Tissue Disease, Department of Inflammation, Division of Medicine, University College London, London, NW3 2PF, UK.
George Bou-GhariosDepartment of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, L7 8TX, UK.
David J AbrahamCentre for Rheumatology and Connective Tissue Disease, Department of Inflammation, Division of Medicine, University College London, London, NW3 2PF, UK.
University College London · GBUniversity of Liverpool · GBCentre for Inflammation Research · GB

Funding

Medical Research Council G0801052Medical Research Council MR/P020941/1Versus Arthritis 19427Versus Arthritis 21810
6 · The paper itself

Abstract

Connective tissue growth factor (CTGF, CCN2) is a matricellular protein which plays key roles in normal mammalian development and in tissue homeostasis and repair. In pathological conditions, dysregulated CCN2 has been associated with cancer, cardiovascular disease, and tissue fibrosis. In this study, genetic manipulation of the CCN2 gene was employed to investigate the role of CCN2 expression in vitro and in experimentally-induced models of pulmonary fibrosis and pulmonary arterial hypertension (PAH). Knocking down CCN2 using siRNA reduced expression of pro-fibrotic markers (fibronectin p < 0.01, collagen type I p < 0.05, α-SMA p < 0.0001, TIMP-1 p < 0.05 and IL-6 p < 0.05) in TGF-β-treated lung fibroblasts derived from systemic sclerosis patients. In vivo studies were performed in mice using a conditional gene deletion strategy targeting CCN2 in a fibroblast-specific and time-dependent manner in two models of lung disease. CCN2 deletion significantly reduced pulmonary interstitial scarring and fibrosis following bleomycin-instillation, as assessed by fibrotic scores (wildtype bleomycin 3.733 ± 0.2667 vs CCN2 knockout (KO) bleomycin 4.917 ± 0.3436, p < 0.05) and micro-CT. In the well-established chronic hypoxia/Sugen model of pulmonary hypertension, CCN2 gene deletion resulted in a significant decrease in pulmonary vessel remodelling, less right ventricular hypertrophy and a reduction in the haemodynamic measurements characteristic of PAH (RVSP and RV/LV + S were significantly reduced (p < 0.05) in CCN2 KO compared to WT mice in hypoxic/SU5416 conditions). These results support a prominent role for CCN2 in pulmonary fibrosis and in vessel remodelling associated with PAH. Therefore, therapeutics aimed at blocking CCN2 function are likely to benefit several forms of severe lung disease.

Indexed as

AnimalsAntibiotics, AntineoplasticBleomycinCells, CulturedCollagen Type IConnective Tissue Growth FactorDisease Models, AnimalGene DeletionHumansMiceMice, KnockoutPulmonary Arterial HypertensionPulmonary FibrosisSignal TransductionTransforming Growth Factor betaAntibiotics, AntineoplasticBleomycinCCN2 protein, humanCCN2 protein, mouseCollagen Type IConnective Tissue Growth FactorTransforming Growth Factor betaBleomycin-induced fibrosisConnective tissue grown factor (CTGF, CCN2)Interstitial lung disease (ILD)Pulmonary arterial hypertension (PAH)Pulmonary fibrosisSystemic sclerosis (scleroderma, SSc)

Identifiers

PMID33662577
PMCPMC8111417
OpenAlexW3134981183

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.