Evidence mapPaperPMID 42278627Full record

ArticleInternational journal of molecular sciences2026

Epithelial PCSK6 Promotes Proliferation and Decreases Collagen Deposition by Fibroblasts Potentially via MMP Activation.

Qian Tian, Annemiek Dijkhuis, Ester B M Remmerswaal, Hella Aberson, Bruno Crestani, Tom van der Poll, C Arnold Spek, Jan Willem Duitman

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In one paragraph

Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
field-weighted citation impact
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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Qian TianDepartment of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0009-0003-0000-8352
Annemiek DijkhuisDepartment of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Ester B M RemmerswaalDepartment of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0003-4694-6048
Hella AbersonCenter for Infection and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Bruno CrestaniService de Pneumologie, Allergologie et Transplantation, Hôpital Bichat Claude Bernard, AP-HP, 75018 Paris, France.ORCID 0000-0002-2961-3455
Tom van der PollCenter for Infection and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
C Arnold SpekCenter for Infection and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0002-2149-4068
Jan Willem DuitmanDepartment of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0003-4254-3380

Funding

China Scholarship Council 202207720069
6 · The paper itself

Abstract

A recent genome-wide association study showed that the protease proprotein convertase subtilisin/kexin type 6 (PCSK6) is highly expressed in idiopathic pulmonary fibrosis (IPF) lung parenchyma and that its expression is associated with disease progression and worse survival. However, whether PCSK6 plays a role in IPF pathophysiology remains elusive. This study aimed to determine whether PCSK6 contributes to IPF pathophysiology, specifically in the cross-talk between epithelial cells and fibroblasts. A549 epithelial cells were transduced with a PCSK6-GFP or control-mCherry vector. Both proliferation (crystal violet) and cell competition assays showed that PCSK6 promoted cell proliferation. Western blot and PCSK-specific fluorogenic substrate assays showed that A549-PCSK6 conditioned medium (CM) had higher PCSK6 enzyme activity compared to mCherry control A549 CM. Human lung fibroblasts stimulated with PCSK6-CM significantly decreased collagen I protein levels as compared to fibroblasts stimulated with control A549-CM. Matrix-metalloproteinase (MMP) specific fluorogenic substrate assays subsequently showed that A549-PCSK6 CM contained higher MMP activity and that PCSK6 inhibition reduced MMP activity in A549-PCSK6 CM, suggesting that PCSK6 plays a role in the activation of MMPs that may degrade collagen type I. In conclusion, epithelial PCSK6 promotes cell proliferation and decreases collagen deposition by fibroblasts, potentially via MMP activation. These in vitro data suggest that PCSK6 could play a dual role in IPF progression and its actual role in IPF should consequently be elucidated using in vivo/ex vivo models.

Indexed as

CollagenCollagen Type IEpithelial CellsFibroblastsMatrix MetalloproteinasesProprotein ConvertasesSerine EndopeptidasesA549 CellsCell ProliferationEnzyme ActivationHumansIdiopathic Pulmonary FibrosisCollagenCollagen Type IMatrix MetalloproteinasesPCSK6 protein, humanProprotein ConvertasesSerine Endopeptidasesalveolar epithelial cellsidiopathic pulmonary fibrosislung fibroblastsmatrix metalloproteinasesproprotein convertase subtilisin/kexin type 6

Identifiers

PMID42278627
PMCPMC13258461

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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 Socratic graph.