ArticleAmerican journal of respiratory cell and molecular biology2018
Extracellular Matrix Cross-Linking Enhances Fibroblast Growth and Protects against Matrix Proteolysis in Lung Fibrosis.
Article in American journal of respiratory cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 157 citations in OpenAlex.
- Pharmacokinetics and Safety Evaluation of the Transglutaminase 2 Inhibitor Suvigletistat in Healthy Chinese, Japanese, and White/European Participants.Clinical pharmacology in drug development · 2026Trial
- Randomized Phase 1 Studies Evaluating the Safety, Tolerability, Pharmacokinetics, and Target Occupancy of Zampilimab in Healthy Participants.Clinical pharmacology in drug development · 2026Trial
- Ginseng as a Functional Food Intervention for Interstitial Lung Disease: A Review of the Benefits and Molecular Mechanisms.Food science & nutrition · 2026Review
- Inhibition of runt related transcription factor 1 with Ro24-7429 improves lung function in experimental models of idiopathic pulmonary fibrosis.Scientific reports · 2026Article
- Dupilumab attenuate IL-4 and IL-13 synergistic effect on airway remodeling in asthma via blocking IL-4Rα/STAT6 axis.Scientific reports · 2026Article
- ATP7A-fibulin-4 complex delivers copper in the Golgi to activate LOX in renal fibrosis.JCI insight · 2026Article
- PBRM1 Deficiency Reshapes an Immune Suppressive Microenvironment Through Epigenetic Tuning of PBRM1-KDM5C-IL6 Axis in ccRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SPECT as a translational non-invasive method to assess occupancy of the tissue transglutaminase-2 by zampilimab in the mouse lung.Respiratory research · 2026Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- Loss of Cathepsin K Impairs Collagen Biogenesis and Enhances Actin Polymerization in Trabecular Meshwork.Investigative ophthalmology & visual science · 2026Article
- Review
- Pancreatic Tissue Remodeling and Fibrosis After Irreversible Electroporation: A Histopathological and Thermal Perspective.Biomedicines · 2025Article
- Transglutaminase 2 in human peritoneal dialysis-related peritoneal injury.Physiological reports · 2025Article
- Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models.Nature communications · 2025Article
- ER O-glycosylation in synovial fibroblasts drives cartilage degradation.Nature communications · 2025Article
- Cardiac function and extracellular matrix morphology are altered by chronic high fat diet in Drosophila larvae.PloS one · 2025Article
- The effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Article
- Role of Lysyl Oxidase-Like Protein 3 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.Investigative ophthalmology & visual science · 2024Article
- Emerging roles of noncoding RNAs in idiopathic pulmonary fibrosis.Cell death discovery · 2024Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by accumulation of extracellular matrix (ECM) proteins and fibroblast proliferation. ECM cross-linking enzymes have been implicated in fibrotic diseases, and we hypothesized that the ECM in IPF is abnormally cross-linked, which enhances fibroblast growth and resistance to normal ECM turnover. We used a combination of in vitro ECM preparations and in vivo assays to examine the expression of cross-linking enzymes and the effect of their inhibitors on fibroblast growth and ECM turnover. Lysyl oxidase-like 1 (LOXL1), LOXL2, LOXL3, and LOXL4 were expressed equally in control and IPF-derived fibroblasts. Transglutaminase 2 was more strongly expressed in IPF fibroblasts. LOXL2-, transglutaminase 2-, and transglutaminase-generated cross-links were strongly expressed in IPF lung tissue. Fibroblasts grown on IPF ECM had higher LOXL3 protein expression and transglutaminase activity than those grown on control ECM. IPF-derived ECM also enhanced fibroblast adhesion and proliferation compared with control ECM. Inhibition of lysyl oxidase and transglutaminase activity during ECM formation affected ECM structure as visualized by electron microscopy, and it reduced the enhanced fibroblast adhesion and proliferation of IPF ECM to control levels. Inhibition of transglutaminase, but not of lysyl oxidase, activity enhanced the turnover of ECM in vitro. In bleomycin-treated mice, during the postinflammatory fibrotic phase, inhibition of transglutaminases was associated with a reduction in whole-lung collagen. Our findings suggest that the ECM in IPF may enhance pathological cross-linking, which contributes to increased fibroblast growth and resistance to normal ECM turnover to drive lung fibrosis.
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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.