ArticleAmerican journal of physiology. Lung cellular and molecular physiology2014
Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels.
Article in American journal of physiology. Lung cellular and molecular physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 214 citations in OpenAlex.
- Article
- An Integrated Therapeutic Strategy for Cardiorenal Syndrome to Target Oxidative Stress, Inflammation, and Fibrosis.Reviews in cardiovascular medicine · 2026Review
- Therapeutic potential of inhibitors of gelatinases MMP-2 and MMP-9 for the treatment of breast cancer.The FEBS journal · 2026Review
- Mechanistic analysis of an IRF7-dependent pathway in virus-induced fibrosis in chronic lung allograft dysfunction.EBioMedicine · 2026Article
- Novel tissue mechanics-guided cellular flows drive the formation of feather follicles.The EMBO journal · 2026Article
- MMP9 Genotype and Systemic T-Cell Subsets Correlate With Structural and Functional Outcomes in Neovascular Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2026Article
- Optical, Tomographic, and Mass Spectrometry Imaging Methods for Burn Wounds: Capabilities, Limitations, and Clinical Potential.Biomedicines · 2026Review
- Neutrophils as critical orchestrators of chronic inflammation.Cellular & molecular immunology · 2026Review
- Computational Elucidation of Hub Genes and Pathways Correlated with the Development of 5-Fluorouracil Resistance in HCT 116 Colorectal Carcinoma Cell Line.Biochemical genetics · 2026Article
- Urinary Biomarkers for Radiation Cystitis: Current Insights and Future Directions.International journal of molecular sciences · 2026Review
- A positive feedback loop between SERPINH1 and MMP-9/TGF-β1 promotes lung adenocarcinoma progression.Cell death and differentiation · 2026Article
- MMP9 regulates osteogenesis and MMP2 expression through the TGF-β1/SMAD2/3 signaling pathway in lipopolysaccharide-induced osteoblasts.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
- Effects of Stiffness and Degradability on Cardiac Fibroblast Contractility and Extracellular Matrix Secretion in Three-Dimensional Hydrogel Scaffolds.ACS biomaterials science & engineering · 2025Article
- ACE-mediated Glycosylation Stabilizes PSAP To Promote GPR37-dependent Macrophage-Nucleus Pulposus Cells Crosstalk and TGFβ Signaling in Alleviating Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Glycolytic Reprogramming in Uterine Fibroids: Genetic, Transcriptomic, Proteomic, and Metabolomic Insights.Genes · 2025Review
- Combinational Therapy of Mesenchymal Stem Cells and Metformin in Bleomycin-Induced Idiopathic Pulmonary Fibrosis in Rat Model.Applied biochemistry and biotechnology · 2025Article
- Molecular Dissection of the Arsenic-Induced Leukocyte Incursion into the Inflamed Thymus and Spleen and Its Amelioration by Co-supplementation of L-Ascorbic Acid and α-Tocopherol.Biological trace element research · 2025Article
- Basic Science Research in Frozen Shoulder: Current Updates.Indian journal of orthopaedics · 2025Article
- Inhibitory effect of MLC901 on axonal demyelination in experimental animals undergoing circumferential lumbal stenosis by increasing transforming growth factor-β1 levels.Asian spine journal · 2025Article
- ZnO colludes with C. acnes in healing delay and Scar hyperplasia by barrier destruction.Journal of nanobiotechnology · 2025Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 4 countries.
Funding
Abstract
Matrix metalloproteinase-9 (MMP-9) is a matrix-degrading enzyme implicated in many biological processes, including inflammation. It is produced by many cells, including fibroblasts. When cultured in three-dimensional (3D) collagen gels, fibroblasts contract the surrounding matrix, a function that is thought to model the contraction that characterizes both normal wound repair and fibrosis. The current study was designed to evaluate the role of endogenously produced MMP-9 in fibroblast contraction of 3D collagen gels. Fibroblasts from mice lacking expression of MMP-9 and human lung fibroblasts (HFL-1) transfected with MMP-9 small-interfering RNA (siRNA) were used. Fibroblasts were cast into type I collagen gels and floated in culture medium with or without transforming growth factor (TGF)-β1 for 5 days. Gel size was determined daily using an image analysis system. Gels made from MMP-9 siRNA-treated human fibroblasts contracted less than control fibroblasts, as did fibroblasts incubated with a nonspecific MMP inhibitor. Similarly, fibroblasts cultured from MMP-9-deficient mice contracted gels less than did fibroblasts from control mice. Transfection of the MMP-9-deficient murine fibroblasts with a vector expressing murine MMP-9 restored contractile activity to MMP-9-deficient fibroblasts. Inhibition of MMP-9 reduced active TGF-β1 and reduced several TGF-β1-driven responses, including activity of a Smad3 reporter gene and production of fibronectin. Because TGF-β1 also drives fibroblast gel contraction, this suggests the mechanism for MMP-9 regulation of contraction is through the generation of active TGF-β1. This study provides direct evidence that endogenously produced MMP-9 has a role in regulation of tissue contraction of 3D collagen gels mediated by fibroblasts.
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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.