ArticleBioengineering (Basel, Switzerland)2023
Substrate Stiffness Modulates TGF-β Activation and ECM-Associated Gene Expression in Fibroblasts.
Article in Bioengineering (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
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.
Who cites it
19 citing papers in PubMed.
- Reprogramming the Tumor Oncobiosphere: Bioactive Nanohybrid Materials for Reversing Therapeutic Pseudo-Resistance.ACS omega · 2026Review
- Nanospider-Generated Polyamide 6 Scaffolds Nanostructured with Graphene Oxide for Enhanced Cell Adhesion and Tissue Development.International journal of molecular sciences · 2026Article
- Latent transforming growth factor binding protein-2 (LTBP2), an IPF biomarker of clinical decline, promotes TGF-beta signaling and lung fibrosis in mice.American journal of respiratory cell and molecular biology · 2026Article
- TGF-β: The Molecular Mechanisms of Atherosclerosis - insights into SMAD Pathways and Gene Therapy Prospects.Current medicinal chemistry · 2026Review
- Mechanical Stiffness Influences the Response of Human Uterine Fibroid Cells to Hormonal Treatments.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- From fibrotic mechanisms to clinical translation: the drug therapy revolution and delivery system breakthrough in proliferative vitreoretinopathy.Frontiers in immunology · 2026Review
- A Trifluoromethyl Quinazoline Compound Regulates the Epithelial-Mesenchymal Transition of Prostatic Hyperplasia Cells by Inhibiting the Secretion of TGF-β1 in Stromal Cells.Current issues in molecular biology · 2025Article
- Nuclear destabilisation - a possible genesis of cancer?Biological reviews of the Cambridge Philosophical Society · 2025Review
- Integrative multi-omics and causal inference reveal periodontal ligament cell-macrophage crosstalk under orthodontic force.Progress in orthodontics · 2025Article
- Role of Growth Factors in the Pathogenesis of Systemic-Sclerosis-Associated Fibrosis.International journal of molecular sciences · 2025Review
- Latent transforming growth factor binding protein-2 (LTBP2), an IPF biomarker of clinical decline, promotes TGF-beta signaling and lung fibrosis in mice.bioRxiv : the preprint server for biology · 2025Article
- Synergistic effects of micropatterned substrates and transforming growth factor-β1 on differentiation of human mesenchymal stem cells into vascular smooth muscle cells through modulation of Krϋppel-like factor 4.In vitro cellular & developmental biology. Animal · 2025Article
- Interplay between MIG-6/papilin and TGF-β signaling promotes extracellular matrix remodeling and modulates the maintenance of neuronal architecture.bioRxiv : the preprint server for biology · 2025Article
- Review
- Decellularized Cell-Secreted Extracellular Matrices as Biomaterials for Tissue Engineering.Small science · 2025Review
- Biomechanical mechanism and clinical management progress of surgical wound tension.Frontiers in surgery · 2025Review
- Biophysical aspects of mechanotransduction in cells and their physiological/biological implications in vocal fold vibration: a narrative review.Frontiers in cell and developmental biology · 2025Review
- GelMA hydrogel dual photo-crosslinking to dynamically modulate ECM stiffness.Frontiers in bioengineering and biotechnology · 2024Article
- Investigating the Impact of Mechanical Properties and Cell-Collagen Interaction on NIH3T3 Function: A Comparative Study on Different Substrates and Culture Environments.Gels (Basel, Switzerland) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-β (TGF-β) is a multifunctional cytokine that regulates the expression of ECM-associated genes during early injury. Tissue fibrosis development is driven by synergistic cues between the evolving biochemical and mechanical milieu. Few studies have addressed the role of substrate stiffness on TGF-β activity and extracellular matrix (ECM)-associated genes. We used a commercial formulation of polydimethylsiloxane (PDMS) to fabricate substrates of 40 kPa, 300 kPa, and 1.5 MPa stiffness, and cultured the HMF3S fibroblasts on substrates. We quantified TGF-β protein secreted by HMF3S cells on different substrates using a TGF-β responsive promoter reporter assay. We also tested for variations in gene expression levels on the substrates using RT-PCR and Western blotting and determined the MMP-2 and MMP-9 activities with gelatin zymography. The results showed that TGF-β protein activation was significantly compromised at lower stiffnesses. The expression of integrin α5 decreased on lower stiffness substrates and correlated with inefficient TGF-β protein activation. Collagen I, collagen III, and MMP-2 expression levels were lower on softer substrates; there was little MMP-9 activity on all substrates. Cell and nuclear morphologies were more rounded on compliant substrates, correlating with increased tubulin expression. Proliferations were higher on stiffer substrates, whereas cells on softer substrates showed cell cycle arrest. These results demonstrated critical feedback mechanisms between substrate stiffness and ECM regulation by fibroblasts, relevant in fibrosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.