Evidence map›Paper›PMID 36408252›Full record

ArticleFrontiers in pharmacology2022

Substrate stiffness engineered to replicate disease conditions influence senescence and fibrotic responses in primary lung fibroblasts.

Kaj E C Blokland, Mehmet Nizamoglu, Habibie Habibie, Theo Borghuis, Michael Schuliga, Barbro N Melgert, Darryl A Knight, Corry-Anke Brandsma, Simon D Pouwels, Janette K Burgess

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

25 citing papers in PubMed, 39 citations in OpenAlex.

  1. Substrate Stiffness and Viscoelasticity Influence Fibroblast Senescence.Journal of biomedical materials research. Part A · 2026
    Article
  2. Article
  3. Review
  4. Review
  5. Article
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  7. The importance of mechanical forces in chronic respiratory diseases.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  8. AdvancingFrontiers in bioengineering and biotechnology · 2026
    Article
  9. Relaxin-2 drives regenerative healing and suppresses scar formation.bioRxiv : the preprint server for biology · 2025
    Article
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  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
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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

10 authors at 4 institutions in 4 countries.

Kaj E C BloklandUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
Mehmet NizamogluUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
Habibie HabibieUniversity of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, Netherlands.
Theo BorghuisUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
Michael SchuligaUniversity of Newcastle, School of Biomedical Sciences and Pharmacy, Callaghan, NSW, Australia.
Barbro N MelgertUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
Darryl A KnightUniversity of Newcastle, School of Biomedical Sciences and Pharmacy, Callaghan, NSW, Australia.
Corry-Anke BrandsmaUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
Simon D PouwelsUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
Janette K BurgessUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
University Medical Center Groningen · NLUniversity of Groningen · NLNational Health and Medical Research Council · AUUniversity of Newcastle Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In fibrosis remodelling of ECM leads to changes in composition and stiffness. Such changes can have a major impact on cell functions including proliferation, secretory profile and differentiation. Several studies have reported that fibrosis is characterised by increased senescence and accumulating evidence suggests that changes to the ECM including altered composition and increased stiffness may contribute to premature cellular senescence. This study investigated if increased stiffness could modulate markers of senescence and/or fibrosis in primary human lung fibroblasts. Using hydrogels representing stiffnesses that fall within healthy and fibrotic ranges, we cultured primary fibroblasts from non-diseased lung tissue on top of these hydrogels for up to 7 days before assessing senescence and fibrosis markers. Fibroblasts cultured on stiffer (±15 kPa) hydrogels showed higher Yes-associated protein-1 (YAP) nuclear translocation compared to soft hydrogels. When looking at senescence-associated proteins we also found higher secretion of receptor activator of nuclear factor kappa-B ligand (RANKL) but no change in transforming growth factor-β1 (TGF-β1) or connective tissue growth factor (CTGF) expression and higher decorin protein deposition on stiffer matrices. With respect to genes associated with fibrosis, fibroblasts on stiffer hydrogels compared to soft had higher expression of smooth muscle alpha (α)-2 actin (

Indexed as

cellular senescencefibrosisGelMA hydrogelsSASPstiffness

Identifiers

PMID36408252
PMCPMC9673045
OpenAlexW4308334532

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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 OpenQuestion graph.