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Latent TGF-β Activation Is a Hallmark of the Tenascin Family
Transforming growth factor-β (TGF-β) isoforms are secreted as inactive complexes formed through non-covalent interactions between bioactive TGF-β entities and their N-terminal pro-domains called latency-associated peptides (LAP). Extracellular activation of latent TGF-β within this complex is a cruc...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155481/ https://www.ncbi.nlm.nih.gov/pubmed/34054795 http://dx.doi.org/10.3389/fimmu.2021.613438 |
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author | Aubert, Alexandre Mercier-Gouy, Perrine Aguero, Stéphanie Berthier, Laurent Liot, Sophie Prigent, Laura Alcaraz, Lindsay B. Verrier, Bernard Terreux, Raphaël Moali, Catherine Lambert, Elise Valcourt, Ulrich |
author_facet | Aubert, Alexandre Mercier-Gouy, Perrine Aguero, Stéphanie Berthier, Laurent Liot, Sophie Prigent, Laura Alcaraz, Lindsay B. Verrier, Bernard Terreux, Raphaël Moali, Catherine Lambert, Elise Valcourt, Ulrich |
author_sort | Aubert, Alexandre |
collection | PubMed |
description | Transforming growth factor-β (TGF-β) isoforms are secreted as inactive complexes formed through non-covalent interactions between bioactive TGF-β entities and their N-terminal pro-domains called latency-associated peptides (LAP). Extracellular activation of latent TGF-β within this complex is a crucial step in the regulation of TGF-β activity for tissue homeostasis and immune cell function. We previously showed that the matrix glycoprotein Tenascin-X (TN-X) interacted with the small latent TGF-β complex and triggered the activation of the latent cytokine into a bioactive TGF-β. This activation most likely occurs through a conformational change within the latent TGF-β complex and requires the C-terminal fibrinogen-like (FBG) domain of the glycoprotein. As the FBG-like domain is highly conserved among the Tenascin family members, we hypothesized that Tenascin-C (TN-C), Tenascin-R (TN-R) and Tenascin-W (TN-W) might share with TN-X the ability to regulate TGF-β bioavailability through their C-terminal domain. Here, we demonstrate that purified recombinant full-length Tenascins associate with the small latent TGF-β complex through their FBG-like domains. This association promotes activation of the latent cytokine and subsequent TGF-β cell responses in mammary epithelial cells, such as cytostasis and epithelial-to-mesenchymal transition (EMT). Considering the pleiotropic role of TGF-β in numerous physiological and pathological contexts, our data indicate a novel common function for the Tenascin family in the regulation of tissue homeostasis under healthy and pathological conditions. |
format | Online Article Text |
id | pubmed-8155481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81554812021-05-28 Latent TGF-β Activation Is a Hallmark of the Tenascin Family Aubert, Alexandre Mercier-Gouy, Perrine Aguero, Stéphanie Berthier, Laurent Liot, Sophie Prigent, Laura Alcaraz, Lindsay B. Verrier, Bernard Terreux, Raphaël Moali, Catherine Lambert, Elise Valcourt, Ulrich Front Immunol Immunology Transforming growth factor-β (TGF-β) isoforms are secreted as inactive complexes formed through non-covalent interactions between bioactive TGF-β entities and their N-terminal pro-domains called latency-associated peptides (LAP). Extracellular activation of latent TGF-β within this complex is a crucial step in the regulation of TGF-β activity for tissue homeostasis and immune cell function. We previously showed that the matrix glycoprotein Tenascin-X (TN-X) interacted with the small latent TGF-β complex and triggered the activation of the latent cytokine into a bioactive TGF-β. This activation most likely occurs through a conformational change within the latent TGF-β complex and requires the C-terminal fibrinogen-like (FBG) domain of the glycoprotein. As the FBG-like domain is highly conserved among the Tenascin family members, we hypothesized that Tenascin-C (TN-C), Tenascin-R (TN-R) and Tenascin-W (TN-W) might share with TN-X the ability to regulate TGF-β bioavailability through their C-terminal domain. Here, we demonstrate that purified recombinant full-length Tenascins associate with the small latent TGF-β complex through their FBG-like domains. This association promotes activation of the latent cytokine and subsequent TGF-β cell responses in mammary epithelial cells, such as cytostasis and epithelial-to-mesenchymal transition (EMT). Considering the pleiotropic role of TGF-β in numerous physiological and pathological contexts, our data indicate a novel common function for the Tenascin family in the regulation of tissue homeostasis under healthy and pathological conditions. Frontiers Media S.A. 2021-05-13 /pmc/articles/PMC8155481/ /pubmed/34054795 http://dx.doi.org/10.3389/fimmu.2021.613438 Text en Copyright © 2021 Aubert, Mercier-Gouy, Aguero, Berthier, Liot, Prigent, Alcaraz, Verrier, Terreux, Moali, Lambert and Valcourt https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Aubert, Alexandre Mercier-Gouy, Perrine Aguero, Stéphanie Berthier, Laurent Liot, Sophie Prigent, Laura Alcaraz, Lindsay B. Verrier, Bernard Terreux, Raphaël Moali, Catherine Lambert, Elise Valcourt, Ulrich Latent TGF-β Activation Is a Hallmark of the Tenascin Family |
title | Latent TGF-β Activation Is a Hallmark of the Tenascin Family |
title_full | Latent TGF-β Activation Is a Hallmark of the Tenascin Family |
title_fullStr | Latent TGF-β Activation Is a Hallmark of the Tenascin Family |
title_full_unstemmed | Latent TGF-β Activation Is a Hallmark of the Tenascin Family |
title_short | Latent TGF-β Activation Is a Hallmark of the Tenascin Family |
title_sort | latent tgf-β activation is a hallmark of the tenascin family |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155481/ https://www.ncbi.nlm.nih.gov/pubmed/34054795 http://dx.doi.org/10.3389/fimmu.2021.613438 |
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