ArticleThe Journal of biological chemistry2008
Focal adhesion kinase (FAK)-related non-kinase inhibits myofibroblast differentiation through differential MAPK activation in a FAK-dependent manner.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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
55 citing papers in PubMed, 90 citations in OpenAlex.
- AI-driven discovery of natural product-derived FAK1 inhibitors for idiopathic pulmonary fibrosis.Molecular diversity · 2026Article
- Particulate matter increases bone morphogenetic protein 2 in lung fibroblasts.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Exploring the role of epigenetics in the processes related to the development of endometrosis in the mare.The Journal of reproduction and development · 2026Review
- FAK-dependent activation of src family kinase member BLK contributed to endometrial fibrosis via endoplasmic reticulum stress.Cell & bioscience · 2025Article
- Development of a high-throughput TR-FRET assay to identify inhibitors of the FAK-paxillin protein-protein interaction.SLAS discovery : advancing life sciences R & D · 2025Article
- State of the ART: Drug Screening Reveals Artesunate as a Promising Anti-Fibrosis Therapy.Journal of respiratory biology and translational medicine · 2025Article
- Mechanisms and Therapeutic Potential of Myofibroblast Transformation in Pulmonary Fibrosis.Journal of respiratory biology and translational medicine · 2025Article
- Two-Pore-Domain Potassium Channel TREK-1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation.Biomedicines · 2023Article
- Hepatocyte phosphatase DUSP22 mitigates NASH-HCC progression by targeting FAK.Nature communications · 2022Article
- Article
- Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis.Acta pharmaceutica Sinica. B · 2022Review
- FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro.Biomolecules · 2021Article
- Titanium Substratum Roughness as a Determinant of Human Gingival Fibroblast Fibronectin and α-Smooth Muscle Actin Expression.Materials (Basel, Switzerland) · 2021Article
- Maintenance of Ligament Homeostasis of Spheroid-Colonized Embroidered and Functionalized Scaffolds after 3D Stretch.International journal of molecular sciences · 2021Article
- Mechanical and Immunological Regulation in Wound Healing and Skin Reconstruction.International journal of molecular sciences · 2021Review
- A novel tree shrew model of pulmonary fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Melatonin ameliorates renal fibroblast-myofibroblast transdifferentiation and renal fibrosis through miR-21-5p regulation.Journal of cellular and molecular medicine · 2020Article
- Neuronal Wiskott-Aldrich syndrome protein regulates Pseudomonas aeruginosa-induced lung vascular permeability through the modulation of actin cytoskeletal dynamics.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Molecular mechanism of tumour necrosis factor alpha regulates hypocretin (orexin) expression, sleep and behaviour.Journal of cellular and molecular medicine · 2019Article
- Wound Healing: A Cellular Perspective.Physiological reviews · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Transforming growth factor (TGF)-beta1 induces fibroblast transdifferentiation to myofibroblasts, a process that requires the involvement of integrin-mediated signaling and focal adhesion kinase (FAK). FAK-related non-kinase (FRNK) is known for its role in inhibiting integrin-mediated cell migration; however, its role in myofibroblast differentiation has not been defined. Here, we report that FRNK abrogates TGF-beta1-induced myofibroblast differentiation in vitro and in vivo. TGF-beta1 can induce alpha-smooth muscle actin (alpha-SMA) expression in the presence or absence of FAK; however, TGF-beta1-induced alpha-SMA expression is reduced (approximately 73%) in FAK-deficient fibroblasts. Although both ERK and p38 MAPK activation is required for maximal TGF-beta1-induced alpha-SMA expression, ERK is the major signaling intermediate in cells that express FAK. In contrast, p38 MAPK is the dominant mediator of TGF-beta1-induced alpha-SMA expression in FAK-deficient cells. FRNK overexpression blocks TGF-beta1-induced ERK or p38 MAPK activation in the presence, and surprisingly, in the absence of FAK. The loss of FRNK was tested in vivo during experimentally induced pulmonary fibrosis in mice. FRNK knock-out mice have a greater increase in alpha-SMA-expressing cells in response to a pulmonary fibrotic stimulus in vivo, as compared with congenic wild type mice. This is the first time that FRNK loss has been shown to modify the pathobiology in any animal disease model. Together, the data demonstrate that FRNK negatively regulates myofibroblast differentiation in vitro and in vivo. These data further suggest that modulation FRNK expression may be a novel avenue for therapeutic intervention in tissue 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.