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Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation
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 forc...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210443/ https://www.ncbi.nlm.nih.gov/pubmed/25332161 http://dx.doi.org/10.1083/jcb.201402006 |
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author | Klingberg, Franco Chow, Melissa L. Koehler, Anne Boo, Stellar Buscemi, Lara Quinn, Thomas M. Costell, Mercedes Alman, Benjamin A. Genot, Elisabeth Hinz, Boris |
author_facet | Klingberg, Franco Chow, Melissa L. Koehler, Anne Boo, Stellar Buscemi, Lara Quinn, Thomas M. Costell, Mercedes Alman, Benjamin A. Genot, Elisabeth Hinz, Boris |
author_sort | Klingberg, Franco |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4210443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-42104432015-04-27 Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation Klingberg, Franco Chow, Melissa L. Koehler, Anne Boo, Stellar Buscemi, Lara Quinn, Thomas M. Costell, Mercedes Alman, Benjamin A. Genot, Elisabeth Hinz, Boris J Cell Biol Research Articles 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. The Rockefeller University Press 2014-10-27 /pmc/articles/PMC4210443/ /pubmed/25332161 http://dx.doi.org/10.1083/jcb.201402006 Text en © 2014 Klingberg et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Klingberg, Franco Chow, Melissa L. Koehler, Anne Boo, Stellar Buscemi, Lara Quinn, Thomas M. Costell, Mercedes Alman, Benjamin A. Genot, Elisabeth Hinz, Boris Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation |
title | Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation |
title_full | Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation |
title_fullStr | Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation |
title_full_unstemmed | Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation |
title_short | Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation |
title_sort | prestress in the extracellular matrix sensitizes latent tgf-β1 for activation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210443/ https://www.ncbi.nlm.nih.gov/pubmed/25332161 http://dx.doi.org/10.1083/jcb.201402006 |
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