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Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation

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Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation

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dc.contributor.author Klingberg, Franco
dc.contributor.author Chow, Melissa L.
dc.contributor.author Koehler, Anne
dc.contributor.author Boo, Stellar
dc.contributor.author Buscemi, Lara
dc.contributor.author Quinn, Thomas M.
dc.contributor.author Costell Rosselló, Mercedes
dc.contributor.author Alman, Benjamin A.
dc.contributor.author Genot, Elisabeth
dc.contributor.author Hinz, Boris
dc.date.accessioned 2016-07-19T15:59:39Z
dc.date.available 2016-07-19T15:59:39Z
dc.date.issued 2014
dc.identifier.citation Klingberg, Franco Chow, Melissa L. Koehler, Anne Boo, Stellar Buscemi, Lara Quinn, Thomas M. Costell Rosselló, Mercedes Alman, Benjamin A. Genot, Elisabeth Hinz, Boris 2014 Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation Journal of Cell Biology 207 2 283 297
dc.identifier.uri http://hdl.handle.net/10550/54633
dc.description.abstract 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.
dc.language.iso eng
dc.relation.ispartof Journal of Cell Biology, 2014, vol. 207, num. 2, p. 283-297
dc.subject Cèl·lules
dc.subject Membranes (Biologia)
dc.title Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation
dc.type journal article es_ES
dc.date.updated 2016-07-19T15:59:40Z
dc.identifier.doi 10.1083/jcb.201402006
dc.identifier.idgrec 111999
dc.rights.accessRights open access es_ES

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