Evidence map›Paper›PMID 36585256›Full record

ArticleThe European respiratory journal2023

Inhibition of MRTF activation as a clinically achievable anti-fibrotic mechanism for pirfenidone.

Hsiao-Yen Ma, Jason A Vander Heiden, Salil Uttarwar, Ying Xi, Elsa-Noah N'Diaye, Ryan LaCanna, Patrick Caplazi, Sarah Gierke, John Moffat, Paul J Wolters and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The European respiratory journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

12 citing papers in PubMed, 22 citations in OpenAlex.

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  11. ANT1 and the SASP: Beyond the Bioenergetic Void.American journal of respiratory cell and molecular biology · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 3 countries.

Hsiao-Yen MaDepartment of Discovery Immunology, Genentech, South San Francisco, CA, USA.
Jason A Vander HeidenDepartment of OMNI Bioinformatics, Genentech, South San Francisco, CA, USA.ORCID 0000-0002-1474-310X
Salil UttarwarDepartment of OMNI Bioinformatics, Genentech, South San Francisco, CA, USA.
Ying XiDepartment of Discovery Immunology, Genentech, South San Francisco, CA, USA.ORCID 0000-0002-1796-3538
Elsa-Noah N'DiayeDepartment of Discovery Immunology, Genentech, South San Francisco, CA, USA.
Ryan LaCannaDepartment of Discovery Immunology, Genentech, South San Francisco, CA, USA.
Patrick CaplaziDepartment of Pathology, Genentech, South San Francisco, CA, USA.ORCID 0000-0002-3411-1257
Sarah GierkeDepartment of Pathology, Genentech, South San Francisco, CA, USA.
John MoffatDepartment of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA, USA.
Paul J WoltersDepartment of Medicine, University of California, San Francisco, CA, USA.
Ning DingDepartment of Discovery Immunology, Genentech, South San Francisco, CA, USA ding.ning@gene.com.ORCID 0000-0001-6560-2967
AbbVie (United States) · USGene Therapy Laboratory · FRGilead Sciences (United States) · USShanghaiTech University · CNUniversity of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease characterised by aberrant fibroblast/myofibroblast accumulation and excessive collagen matrix deposition in the alveolar areas of lungs. As the first approved IPF medication, pirfenidone (PFD) significantly decelerates lung function decline while its underlying anti-fibrotic mechanism remains elusive.

methodsWe performed transcriptomic and immunofluorescence analyses of primary human IPF tissues.

resultsWe showed that myocardin-related transcription factor (MRTF) signalling is activated in myofibroblasts accumulated in IPF lungs. Furthermore, we showed that PFD inhibits MRTF activation in primary human lung fibroblasts at clinically achievable concentrations (half-maximal inhibitory concentration 50-150 µM, maximal inhibition >90%, maximal concentration of PFD in patients <100 µM). Mechanistically, PFD appears to exert its inhibitory effects by promoting the interaction between MRTF and actin indirectly. Finally, PFD-treated IPF lungs exhibit significantly less MRTF activation in fibroblast foci areas than naïve IPF lungs.

conclusionsOur results suggest MRTF signalling as a direct target for PFD and implicate that some of the anti-fibrotic effects of PFD may be due to MRTF inhibition in lung fibroblasts.

Indexed as

Idiopathic Pulmonary FibrosisTranscription FactorsFibroblastsFibrosisHumansLungMyocardinMyofibroblastsPyridonesTrans-ActivatorsMyocardinpirfenidonePyridonesTrans-ActivatorsTranscription Factors

Identifiers

PMID36585256
PMCPMC10133585
OpenAlexW4313318686

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.