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2014
- doi: 10.1083/jcb.201402006
- issn: 0021-9525
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Intercellular matrix Matrix, Extracellular Ground substance (Anatomy) Ground substance (Histology) Interstitial substance Cement substance (Anatomy)Citer ce document
F. Klingberg et al., « Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation. », Serveur académique Lausannois, ID : 10.1083/jcb.201402006
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Integrin-mediated force application induces a conformational change in latent TGF-β1 that leads to the release of the active form of the growth factor from the extracellular matrix (ECM). Mechanical activation of TGF-β1 is currently understood as an acute process that depends on the contractile force of cells. However, we show that ECM remodeling, preceding the activation step, mechanically primes latent TGF-β1 akin to loading a mechanical spring. Cell-based assays and unique strain devices were used to produce a cell-derived ECM of controlled organization and prestrain. Mechanically conditioned ECM served as a substrate to measure the efficacy of TGF-β1 activation after cell contraction or direct force application using magnetic microbeads. The release of active TGF-β1 was always higher from prestrained ECM as compared with unorganized and/or relaxed ECM. The finding that ECM prestrain regulates the bioavailability of TGF-β1 is important to understand the context of diseases that involve excessive ECM remodeling, such as fibrosis or cancer.