Evidence map›Paper›PMID 29703175›Full record

ArticleBMC pulmonary medicine2018

Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells.

M Molina-Molina, C Machahua-Huamani, V Vicens-Zygmunt, R Llatjós, I Escobar, E Sala-Llinas, P Luburich-Hernaiz, J Dorca, A Montes-Worboys

Open access · goldAbstract read
In one paragraph

Article in BMC pulmonary medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
5.9field-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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.

  1. Pooled it
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  17. Silicosis: from pathogenesis to therapeutics.Frontiers in pharmacology · 2025
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  18. Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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6 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

9 authors at 5 institutions in 1 country.

M Molina-MolinaDepartment of Pneumology, Bellvitge University Hospital, Barcelona, Spain.
C Machahua-HuamaniPneumology Research Group, IDIBELL, University of Barcelona, Barcelona, Spain.
V Vicens-ZygmuntDepartment of Pneumology, Bellvitge University Hospital, Barcelona, Spain.
R LlatjósDepartment of Pathology, Bellvitge University Hospital, Barcelona, Spain.
I EscobarDepartment of Thoracic Surgery, Bellvitge University Hospital, Barcelona, Spain.
E Sala-LlinasResearch Network in Respiratory Diseases (CIBERES), ISCIII, Madrid, Spain.
P Luburich-HernaizServei de Diagnostic per la Imatge El Prat (SDPI El Prat) Department of Radiology, Bellvitge University Hospital, Barcelona, Spain.
J DorcaDepartment of Pneumology, Bellvitge University Hospital, Barcelona, Spain.
A Montes-WorboysDepartment of Pneumology, Bellvitge University Hospital, Barcelona, Spain. amontesw@idibell.cat.
Bellvitge University Hospital · ESInstitut d'Investigació Biomédica de Bellvitge · ESUniversitat de Barcelona · ESHospital Universitario Son Espases · ESInstituto de Salud Carlos III · ES

Funding

Instituto de Salud Carlos III FIS PI15/00710
6 · The paper itself

Abstract

backgroundPirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the effects of pirfenidone.

methodsPrimary lung fibroblasts from IPF patients and human alveolar epithelial cells (A549) were treated in vitro with pirfenidone and rapamycin in the presence or absence of transforming growth factor β1 (TGF-β). Extracellular matrix protein and gene expression of markers involved in lung fibrosis (tenascin-c, fibronectin, collagen I [COL1A1], collagen III [COL3A1] and α-smooth muscle actin [α-SMA]) were analyzed. A cell migration assay in pirfenidone, rapamycin and TGF-β-containing media was performed.

resultsGene and protein expression of tenascin-c and fibronectin of fibrotic fibroblasts were reduced by pirfenidone or rapamycin treatment. Pirfenidone-rapamycin treatment did not revert the epithelial to mesenchymal transition pathway activated by TGF-β. However, the drug combination significantly abrogated fibroblast to myofibroblast transition. The inhibitory effect of pirfenidone on fibroblast migration in the scratch-wound assay was potentiated by rapamycin combination.

conclusionsThese findings indicate that the combination of pirfenidone and rapamycin widen the inhibition range of fibrogenic markers and prevents fibroblast migration. These results would open a new line of research for an anti-fibrotic combination therapeutic approach.

Indexed as

A549 CellsAlveolar Epithelial CellsBiomarkersCell MovementEpithelial-Mesenchymal TransitionExtracellular MatrixHumansIdiopathic Pulmonary FibrosisMyofibroblastsPyridonesSirolimusTransforming Growth Factor beta1BiomarkerspirfenidonePyridonesSirolimusTransforming Growth Factor beta1Cell migrationEpithelial-mesenchymal transitionExtracellular matrix proteinsIdiopathic pulmonary fibrosisPirfenidonePulmonary fibrosisRapamycin

Identifiers

PMID29703175
PMCPMC5922028
OpenAlexW2807553755

What OpenQuestion holds

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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.