ArticlePloS one2014
Regulation of the innate immune response by fibronectin: synergism between the III-1 and EDA domains.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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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.
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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.
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Who cites it
58 citing papers in PubMed, 93 citations in OpenAlex.
- Article
- A Dusty Affair: SIRT1-S682 Modulation Orchestrates ERK-FN1-p38-NF-κB Signaling and Composite-Dependent IL-8 Responses in Gingival Keratinocytes Exposed to Dental Dust and Eluates.Journal of functional biomaterials · 2026Article
- Matrix molecules associated with both regulation of inflammation and pathogenic outcomes associated with the surface of the lens in the eyes of EAU mice.Experimental eye research · 2025Article
- Shared Phenotypes of Immune Cells Recruited to the Cornea and the Surface of the Lens in Response to Formation of Corneal Erosions.The American journal of pathology · 2025Article
- EDA Fibronectin Microarchitecture and YAP Translocation during Wound Closure.ACS biomaterials science & engineering · 2025Article
- The Chromosome-level Genome of the Ctenophore Mnemiopsis leidyi A. Agassiz, 1865 Reveals a Unique Immune Gene Repertoire.Genome biology and evolution · 2025Article
- Delivery technologies for therapeutic targeting of fibronectin in autoimmunity and fibrosis applications.Advanced drug delivery reviews · 2024Review
- Mechanobiology of Type 1 hypersensitivity: Elucidating the impacts of mechanical forces in allergic reactions.Mechanobiology in medicine · 2024Review
- Complement Cascade Proteins Correlate with Fibrosis and Inflammation in Early-Stage Type 1 Diabetic Kidney Disease in the Ins2Akita Mouse Model.International journal of molecular sciences · 2024Article
- Extracellular Matrix-Derived Damage-Associated Molecular Patterns (DAMP): Implications in Systemic Sclerosis and Fibrosis.The Journal of investigative dermatology · 2023Review
- Fibronectin-targeted FUD and PEGylated FUD peptides for fibrotic diseases.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID.medRxiv : the preprint server for health sciences · 2023Article
- Induction of pro-inflammatory genes by fibronectin DAMPs in three fibroblast cell lines: Role of TAK1 and MAP kinases.PloS one · 2023Article
- Mineralocorticoid receptor antagonists and glucocorticoids differentially affect skeletal muscle inflammation and pathology in muscular dystrophy.JCI insight · 2022Article
- Serum Proteome Signatures of Anti-SARS-CoV-2 Vaccinated Healthcare Workers in Greece Associated with Their Prior Infection Status.International journal of molecular sciences · 2022Article
- Angiogenesis is critical for the exercise-mediated enhancement of axon regeneration following peripheral nerve injury.Experimental neurology · 2022Article
- Article
- ITRAQ-based quantitative proteomics analysis of forest musk deer with pneumonia.Frontiers in veterinary science · 2022Article
- Microenvironmental modulation of the developing tumour: an immune-stromal dialogue.Molecular oncology · 2021Review
- The RNA binding protein Quaking represses splicing of the Fibronectin EDA exon and downregulates the interferon response.Nucleic acids research · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Fibronectin is a critical component of the extracellular matrix and alterations to its structure will influence cellular behavior. Matrix fibronectin is subjected to both mechanical and biochemical regulation. The Type III domains of fibronectin can be unfolded in response to increased cellular contractility, included or excluded from the molecule by alternative splicing mechanisms, or released from the matrix by proteolysis. Using Inflammatory Cytokine microarrays we found that the alternatively spliced fibronectin Type III domain, FnEDA, and the partially unfolded III-1 domain, FnIII-1c, induced the expression of a multitude of pro-inflammatory cytokines in human dermal fibroblasts, most notably CXCL1-3, IL-8 and TNF-α. FnIII-1c, a peptide representing an unfolded intermediate structure of the first Type III domain has been shown to initiate the toll-like receptor-4 (TLR4)-NFκB-dependent release of cytokines from human dermal fibroblasts (You, et al., J. Biol. Chem., 2010). Here we demonstrate that FnIII-1c and the alternatively spliced FnEDA domain induce a TLR4 dependent activation of p38 MAP kinase and its downstream effector, MAPKAP Kinase-2 (MK-2), to regulate cytokine expression in fibroblasts. RT-qPCR analysis indicated that the p38-MK-2 pathway regulates IL-8 mRNA stability. Interestingly, addition of FnIII-1c and FnEDA synergistically enhanced TLR4-dependent IL-8 release. These data indicate that Fn contains two Type III domains which can activate TLR signaling to induce an inflammatory response in fibroblasts. Furthermore, our data identifies the NF-κB and p38/MK2 signaling pathways as transducers of signals initiated in response to structural changes in fibronectin.
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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.